Annuloplasty procedures, related devices and methods

ABSTRACT

Devices and methods are disclosed for the treatment or repair of regurgitant cardiac valves, such as a mitral valve. An illustrative annuloplasty device can be placed in the coronary sinus to reshape the mitral valve and reduce mitral valve regurgitation. The disclosure also provides improved techniques for cardiac pacing.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present patent application is a continuation of and claims thebenefit of priority to International Application No. PCT/US18/48172,filed Aug. 27, 2018, which in turn claims the benefit of priority toU.S. patent application Ser. No. 15/796,344, filed Oct. 27, 2017, nowU.S. Pat. No. 10,433,962, issued Oct. 8, 2019, U.S. Provisional PatentApplication Ser. No. 62/663,903, filed Apr. 27, 2018, U.S. ProvisionalPatent Application Ser. No. 62/550,583, filed Aug. 26, 2017, and U.S.Provisional Patent Application Ser. No. 62/615,309, filed Jan. 9, 2018.The present patent application is a continuation-in-part of and claimsthe benefit of priority to U.S. patent application Ser. No. 15/796,344,filed Oct. 27, 2017, now U.S. Pat. No. 10,433,962, issued Oct. 8, 2019,which in turn is a continuation-in-part of and claims the benefit ofpriority to PCT/US2017/031543, filed May 8, 2017, which in turn claimsthe benefit of priority to U.S. Provisional Patent Application Ser. No.62/332,754, filed May 6, 2016. The disclosure of each of the foregoingpatent applications is expressly incorporated by reference herein forany purpose whatsoever.

FIELD OF THE DISCLOSURE

The present disclosure relates to annuloplasty techniques and devices inwhich tensioning elements (e.g., tethers) are placed in the coronarysinus to perform mitral valve annuloplasty and treat mitral valveregurgitation.

BACKGROUND

Traditional mitral valve annuloplasty requires open heart surgery with asternotomy or thoracotomy and cardiac arrest and cardio-pulmonarybypass. For example, the annuloplasty procedure is performed through asurgical incision in which the effective size of the valve annulus isreduced by attaching a prosthetic annuloplasty ring to the left atrialaspect of the mitral valve annulus. A variety of rigid and flexibleannuloplasty rings have been developed for this purpose, such as thoseshown in U.S. Pat. Nos. 4,917,698; 5,041,130; 5,061,277; 5,064,431;5,104,407; 5,201,880; and 5,350,420. Although very effective, thisopen-heart procedure is accompanied by substantial morbidity andprolonged convalescence. As a result, the procedure often is not offeredto patients who are insufficiently symptomatic to justify the surgicalrisk and morbidity, or to patients who suffer advanced disease, or topatients with substantial co-morbidity.

Percutaneous approaches to mitral valve repair have been developed toreduce the clinical disadvantages of the open-heart procedures. But,these procedures suffer from various drawbacks. InternationalApplication No. PCT/US2017/031543, filed May 8, 2017, related to thepresent disclosure, presents considerable improvements over the state ofthat prior art. In some aspects, the present disclosure provides stillfurther improvements over the prior art.

In other aspects, the present disclosure provides improvements in thearea of pacing. Since a pacemaker was first introduced by Furman andRovinson in 1958, the pacemaker has been used as an important device fortreating patients with bradyarrhythmia. Pacemakers are usually used intreatments for arrhythmia such as complete atrioventricular block, highdegree atrioventricular block, and sinus node dysfunction accompanied bysymptoms. A treatment using a pacemaker is a method that artificiallyprovides an electrical stimulus when an electrical stimulus is notnormally transmitted to a heart, and/or when an incorrect stimulus istransmitted to the heart.

FIGS. 1A-1C are views of a conduction system of a human heart, in whichFIG. 1A shows a flow in a conduction system, FIG. 1B shows a waveform inan electrocardiogram, and FIG. 1C illustrates the relationship between aconduction process and a waveform. As discussed in U.S. patentapplication Ser. No. 15/328,046, filed Jun. 16, 2015 (incorporated byreference herein in its entirety for any purpose whatsoever), anelectrical stimulus is transmitted to the overall ventricles through aconduction pathway after passing through a sinoatrial (SA) node, anatrioventricular (AV) node in the atriums and then passing through thebundle of His and a bundle branch in the ventricles.

In an electrocardiogram, a QRS-complex is generated by a depolarizationprocess of ventricular muscles. The first downward wave following aP-wave is called a Q-wave, the first upward wave is called an R-wave,and the downward wave following the R-wave is called an S-wave. Thewidth of the QRS indicates the time taken for electricity to beconducted throughout the ventricles. The width of the QRS is typicallywithin about 0.12 seconds (around about 90 ms) in a normal state, butwhen it is 0.12 seconds or more, it indicates the presence of aninterventricular conduction defect.

A pacemaker is generally composed of a generator and a lead. Thegenerator supplies power and includes a controller with processingcircuitry as well as detection circuitry for detecting operationalaspects of the heart. The pacemaker typically supplies power or suspendspower, depending on the state of operation of the heart. Power isselectively applied to the heart by way of the lead, which terminates inan electrode. Pacemakers typically operate in a bipolar manner, meaningthat the lead actually includes two electrodes—one for deliveringelectrons (anode) and one for absorbing electrons (cathode). However,the cathode is typically considered to be the hot lead for purposes ofconvention. In the event the anode breaks or ceases to function, thepacemaker controller will detect this and then operate the device as amonopolar device, wherein the anode becomes the casing and the “hot”lead continues to act as a cathode.

According to a common treatment that is performed by a pacemaker atpresent, the tip of the lead of a pacemaker is inserted and fixed in theapex of the right ventricle (RV apex) of ventricles and then electricalstimulus is provided. This is called right ventricular apical pacing(RVAP). In RVAP, the electrical stimulus at the RV apex is nottransmitted through the conduction system of the heart that quicklytransmits electrical stimulus in a ventricle. It is instead transmittedthrough cariomyocytes of the ventricle that relatively slowly transmitelectrical stimulus. Consequently, it can take a relatively long timefor the electrical stimulus to spread through the entire ventricle. Thiscan be expected to (and typically does) result in an increase of QRSwidth, which results in ventricular desynchronization, and reduces thepumping efficiency of the heart. Ideally, the ventricles are contractedat the same time for better efficiency.

To address this, attempts have been made to position the electrode ofthe pacemaker lead at a right ventricular basal septum and applyingelectrical stimulus around the nerve bundles that precipitateventricular contraction. This is referred to as right ventricular septalpacing (RVSP). The RVSP is most usually used at the interventricularseptum of a right ventricular outflow tract (RVOT). RVSP theoreticallycompensates for the defects of the RVAP, but in the actual operation itis difficult to accurately position the lead of a pacemaker at theinterventricular septum around the RVOT and the lead may be separated ormoved, so the operation itself is difficult and accordingly it is notgenerally used. The RVSP has another characteristic that positions thelead tip at an interventricular septum, but stimulates not the inside,but the outer side of the interventricular septum, and it is known thatthe RVSP is less effective than the method of stimulating theendocardium or the center of an interventricular septum.

Another method of obtaining a narrower QRS is applied to a case when apatient with heart failure accompanied by ventricular insufficiency hasa wide QRS in an electrocardiogram. This method uses two leads, andpositions a lead at an RV apex and applies electrical stimulus andpositions the other lead at a left lateral vein and applies electricalstimulus to a side of the left ventricle. This treatment seeks to obtaina narrower QRS by simultaneously applying electrical stimulus to the RVapex and the side of the left ventricle. This is referred to as “CardiacResynchronization Therapy (CRT)”. CRT is a very effective treatment whena patient with heart failure has LBBB (left bundle branch block).However, CRT has a deficiency in that it needs to use two leads forstimulating ventricles in order to obtain a narrower QRS.

Intraseptal pacing that can apply direct electrical stimulus to aninterventricular septum has been attempted. For example, methods byforcibly positioning the lead of a pacemaker into the interventricularseptum directly through the left ventricle from the right ventricle havebeen disclosed in US2010/0298841 and US 2013/0231728. These methods havehigh invasion depth that causes an artificial loss of interventricularseptum between the left and right ventricles, have a high possibility oftearing surrounding tissues during the operation, and have a highpossibility of causing an embolism due to air or blood clots. Further,these methods have many dangers and limits, for example, it can locallyapproach the middle portion or the apex of ventricles rather than thebase which is preferable. U.S. Ser. No. 15/328,046 attempts to improveon the state of the art by a further approach intended to address thedeficiencies in the aforementioned approaches. The present disclosureprovides additional improvements over the state of the art.

SUMMARY OF THE DISCLOSURE

In a majority of humans, the coronary vein crosses over the leftcircumflex (“LCx”) artery, which has limited the usefulness of coronarysinus annuloplasty. Some techniques for addressing this are described,for example, in U.S. Pat. No. 9,271,833, and U.S. patent applicationSer. No. 15/056,599, filed Feb. 29, 2016, each of which is incorporatedby reference herein in its entirety for any purpose whatsoever. Furtherimprovements are detailed in U.S. patent application Ser. No.15/796,344. The present disclosure provides still further improvementsin such techniques and related devices to enhance the reliability andefficacy of cerclage procedures.

In particular embodiments, the disclosure provides implementations of animplant that includes a bridge having a proximal end, a distal end, andan arched portion defined between the proximal end and the distal end ofthe bridge. The bridge defines an upwardly facing surface from theproximal end to the distal end of the bridge. The implant furtherincludes an elongate inner tether disposed on the upwardly facingsurface from the proximal end to the distal end of the bridge. Theelongate inner tether is coupled to the bridge to maintain the relativeposition of the elongate inner tether to the bridge. The implant furtherincludes an outer sheath material surrounding and encasing the bridgeand elongate inner tether.

If desired, at least one of the elongate inner tether and the outersheath material can include radiopaque material along its length. Theradiopaque material within the elongate inner tether can include aradiopaque wire disposed within a length of heat shrunk polymeric tubethat resides within a hollow core of the elongate inner tether. Theelongate inner tether can be coupled to the bridge by a polymeric tubethat is shrunk around and in direct physical contact with the bridge andthe inner elongate tether, the polymeric tube extending axially beyondthe proximal end and the distal end of the bridge. The outer sheathmaterial can include a hollow suture material that extends proximallyand distally beyond the polymeric tube. Portions of the polymeric tubecan extend beyond the proximal end and the distal end of the bridge actas a strain relief to provide a transition in stiffness of the implantfrom the bridge to the outer sheath material. The outer sheath materialcan include a hollow suture material that extends proximally anddistally beyond the bridge. If desired, the implant can further includea strain relief tube shrunk around the proximal and distal ends of thebridge, wherein the strain relief tubes hold the inner tether in placewith respect to the bridge.

In various implementations, the bridge can be formed from shape memorymaterial and can be configured to facilitate vertical compression of thearch portion of the bridge to lower the profile of the bridge from afirst height to a second, lower height to facilitate introduction of thebridge into a percutaneous delivery system, wherein the arch portion ofthe bridge is configured to self-expand to the first height after it isdeployed from the delivery system. For example, the shape memorymaterial can be in the shape of a flat wire.

If desired, the implant can further include a selectively removableproximal delivery tube disposed over the outer sheath material, a distalend of the proximal delivery tube abutting near a proximal end region ofthe bridge, and/or a selectively removable distal delivery tube disposedover the outer sheath material, a proximal end of the distal deliverytube abutting near a distal end region of the bridge. The implant canfurther include an implant lock, wherein opposite ends of the outersheath material are directed through the implant lock, and furtherwherein the implant lock is configured to maintain the length of theouter sheath material when installed in a heart. The implant lock candefine at least one distal opening therein. The at least one distalopening can be connected to two distally extending tubular limbs forguiding the outer sheath material therethrough. A first of the tubularlimbs can be configured to traverse the tricuspid valve and can includean atraumatic distal tip formed thereon for distributing axially appliedstress across a surface of a native septum after traversing thetricuspid valve. The first tubular limb can be configured to permit theouter sheath material to pass therethrough. A second of the tubularlimbs can be configured to traverse the coronary sinus and is configuredto permit the outer sheath material to pass therethrough. The first andsecond tubular limbs can each be polymeric tubes preformed with acurvature of about 90 degrees along their lengths to approximate thevascular anatomy that they traverse to reduce applied thereto. At leastone of the limbs can be an adjustable limb having an adjustable length,wherein the length of said at least one adjustable limb can be adjustedwhile it is being urged against native anatomy. If desired, at least oneof said tubular limbs can include a detachable portion that can bereplaced with a different detachable portion of a different length. Insome embodiments, a distal region of the outer sheath material can becrimped to a distal end of the distal delivery tube by a crimp thatcompresses the distal delivery tube against the outer sheath material.

The disclosure further provides a method of implanting an implant as setforth herein, including directing a distal end of a guidewire at leastpartially through a coronary sinus of a heart and over a coronary arteryand into the right ventricle or the right atrium, withdrawing the distalend of the guidewire from the patient such that the proximal and distalends of the guidewire are outside the patient, and the guidewiretraverses a loop shaped path through the heart by way of the coronarysinus to surround a native mitral valve, and crimping the crimp of animplant as set forth herein to a proximal end of the guidewire. Themethod can further include advancing the implant until the archedportion of the bridge of the implant straddles the LCx artery bymanipulating the delivery tubes, withdrawing the delivery tubes from theouter sheath material. fixating the implant in place to maintain thelength of the sheath by advancing a re-fastenable lock along opposingends of the outer sheath material, through the patient's vasculature andinto the patient's heart, wherein the lock is fastened within thepatient's heart, and cutting excess outer sheath material that passesthrough a proximal portion of the lock.

If desired, the method can further include implanting a transcatheterprosthetic mitral valve within a native mitral valve region, wherein theprosthetic mitral valve applies an outward expansion force on myocardiumunderlying the coronary artery, and further wherein the bridge inhibitsapplication of compressive pressure to the coronary artery by theprosthetic mitral valve. The method can further include loading theimplant into an implant loader to reduce the profile of a bridge, andthen introducing the implant into a delivery system prior to introducingthe implant into the patient. The method can further include withdrawinga distal sheath of the delivery system to permit the bridge of theimplant to expand.

The disclosure further provides an implant that includes an elongateinner tether having a proximal end and a distal end, an outer sheathmaterial surrounding the elongate inner tether, a selectively removableproximal delivery tube disposed over or within the outer sheath materialand surrounding a proximal portion of the elongate inner tether, adistal end of the proximal delivery tube being located within a centralregion of the outer sheath, and a selectively removable distal deliverytube disposed over or within the outer sheath material and surrounding adistal portion of the elongate inner tether, a proximal end of thedistal delivery tube being located within the central region of theouter sheath.

If desired, the method can further include implanting a transcatheterprosthetic mitral valve within the native mitral valve region, whereinthe prosthetic mitral valve applies an outward expansion force onmyocardium underlying the coronary artery, and further wherein thebridge (or other stiffened portion of the implant) inhibits applicationof compressive pressure to the coronary artery by the prosthetic mitralvalve. The method may include releasing the tension in the sheathmaterial of the implant, repositioning the implant, and reapplying thetension to the sheath material. Any suitable amount of tension can beapplied to the implant in order to effectuate the desired outcome.

The disclosure still further provides embodiments of a snare catheterthat includes an elongate core member having a proximal end and a distalend, an elongate intermediate tubular member having a proximal end, adistal end and defining an elongate lumen therethrough for slidablyreceiving the elongate core member therein, a collapsible tubularperforated body formed from a plurality of parallel, radially inwardlycollapsible elongate members attached at a proximal end thereof to thedistal end of the elongate intermediate tubular member, and at a distalend thereof to the distal end of the elongate core member, whereinrelative axial displacement of the distal end of the elongateintermediate tubular member toward the distal end of the elongate coremember causes the elongate members to expand radially outwardly and tomutually separate, and relative axial displacement of the distal end ofthe elongate intermediate tubular member away from the distal end of theelongate core member causes the elongate members to collapse radiallyinwardly and to collapse together. The snare catheter can furtherinclude a target wire disposed within a central region of thecollapsible elongate members that extends along the elongate core memberand has a proximal end attached to the elongate intermediate tubularmember and a distal end attached to the elongate core member. The targetwire can be configured to assume a first generally straightconfiguration when the collapsible elongate members is collapsedradially inwardly, and a second substantially nonlinear configurationwhen the collapsible elongate members are expanded radially outwardly.The snare catheter can further include an elongate tubularlongitudinally displaceable sheath having a proximal end, a distal endand defining an elongate lumen therethrough for slidably receiving theelongate core member, elongate intermediate tubular member, collapsibleelongate members, and target wire therein when the collapsible elongatemembers are in a generally radially collapsed state.

If desired, the elongate core member of the snare catheter can be atubular member defining a guidewire lumen therethrough. The snarecatheter can be provided with an atraumatic distal tip formed fromcompliant material that is attached to the distal end of the elongatecore member. The snare catheter (or any device described herein) canfurther include radiopaque marker bands disposed near the distal end ofthe catheter and the distal end of the elongate intermediate tubularmember. If desired, the snare catheter can include a plurality ofradiopaque marker bands formed on the target wire. The target wire canbe formed at least in part from radiopaque material. The collapsibletubular perforated body can be formed at least in part from radiopaquematerial.

In some implementations, the target wire can include at least one loopand/or undulation formed therein when it is longitudinally contracted.If desired, the target wire can include a plurality of loops and/orundulations formed therein when it is longitudinally contracted. Thetarget wire and loop (and/or undulation) can substantially lay in asingle plane parallel to a longitudinal axis of the catheter when thetarget wire is longitudinally contracted. The target wire and loop(s)and/or undulation(s) can define a three dimensional geometry when thetarget wire is longitudinally contracted. If desired, a plurality oftarget wires can be provided having one or more loops and/or undulationswhen the target wires are longitudinally contracted. The target wire caninclude composite wire, such as a wire that includes a core portion madefrom a first material, and a cladding portion made from a secondmaterial different from the first material.

The disclosure further provides a lock delivery catheter that includesan elongate inner tubular member having a proximal end and a distal end,an elongate outer tubular member having a proximal end, a distal end anddefining an elongate lumen therethrough for slidably receiving theelongate inner tubular member therein, and a deployable lock attached tothe lock delivery catheter including a lock body and a wedge, the wedgebeing configured to wedge against the lock body when the lock body andwedge are pressed together.

The lock body is typically detachably attached to the distal end of theelongate outer tubular member, and the wedge is typically detachablyattached to the distal end of the elongate inner tubular member. Thelock delivery catheter can further include at least one guiding suturerouted between the lock body and the wedge and extending proximallythrough the elongate inner tubular member. The at least one guidingsuture can be a snare suture including a loop formed at a distal endthereof for attaching to a second suture (e.g., one or both ends of theimplant) to facilitate drawing the second suture through the lockdelivery catheter. The lock body can include a pin that spans the lockbody, and the pin can pass through a portion of the wedge to couple thelock body to the wedge. The pin can pass through a longitudinal grooveformed into the wedge, such that the lock body and wedge can slide withrespect to each other along the longitudinal groove. The wedge caninclude a proximal portion defining a proximal opening that extends intoa central passage in the proximal portion that divides into two passagesthat terminate at two distal openings defined in two surfaces that layon either side of an elongate portion of the wedge that defines alongitudinal slot therein. Each of the two distal openings each caninclude a suture passing therethrough that extend proximally through theelongate inner tubular member and distally between the lock body and thewedge. The lock body can define a distal opening for routing at leastone suture therethrough. The distal opening of the lock body can includeat least one distally extending sleeve disposed therein for guiding asuture therethrough. The distal opening of the lock body can include twodistally extending sleeves disposed therein for guiding a suturetherethrough. At least one of the sleeves can include two concentricsleeves that cooperate to form a telescoping sleeve capable of beingadjustable to more than one length. At least one of the sleeves caninclude an atraumatic distal tip formed thereon. If desired, at leastone of the sleeves can include an opening formed through a wall thereofconfigured to permit a tether to pass therethrough, rather than havingthe tether traverse the full length of the sleeve.

In some implementations, the lock delivery catheter can further includea handle attached to a proximal portion of the outer tubular member thatcan be provided with one or more actuators. The lock delivery cathetercan be provided with a tether loop routed through a portion of the lockbody and extending proximally to a tether clamp, the tether loop beingconfigured to hold the lock body fast against a distal end of the outertubular member. The handle can be provided with at least one springloaded clamp configured to selectively maintain tension on a tether ofan implant, or on any other desired filament. In some implementations,the distal end of the outer tubular member can be configured tointerdigitate with the lock body so that the outer tubular member cantransmit torque to the lock body. If desired, the distal end of theouter tubular member can be shaped to guide the lock body into thedistal end of the outer tubular member.

The disclosure further provides a cutting catheter that can include anelongate inner member having a proximal end and a distal end with adistally facing blade mounted on the distal end, and an elongate outertubular member having a proximal end, a distal end and defining anelongate lumen therethrough for slidably receiving the elongate innertubular member therein, wherein the elongate outer tubular memberdefines a pair of laterally offset holes therethrough near the blade forreceiving a suture material therethrough, wherein distal advancement ofthe elongate inner member with respect to the elongate outer tubularmember passes the blade past the suture to cut the suture. If desired,the distally facing blade can be mounted on a generally planar distalregion of the elongate inner member that is configured to slide within aflattened distal portion of the elongate outer tubular member. A styletmay also be provided that is fed through the pair of laterally offsetholes for initially capturing the suture material, the end of theimplants, or other tether.

The disclosed devices may be used in methods of improving the functionof a mitral valve in a subject in which an annuloplasty element, forexample an element that exerts compressive tensile remodeling forces onthe mitral valve (such as a tensioning element), is introduced at leastpartially around the mitral valve, for example at least partiallythrough the coronary sinus and over a coronary artery. The protectivedevice is placed between the annuloplasty element and the coronaryartery, with the annuloplasty element separated from the underlyingcoronary artery by the bridge of the device. Reinforcing core elementscan then be removed from the device and a lock can be introduced overthe device and advanced to a location where it can maintain tension onthe implant.

Compressive remodeling forces are exerted by the annuloplasty device(for example by applying tension on a tensioning element to alter theshape or configuration of the mitral valve annulus to reduce itscircumference) while supporting the annuloplasty element on the bridgeto inhibit application of pressure to the coronary artery. The functionof the mitral valve in the patient is thereby improved without impairingcoronary blood flow.

In one example of a method in accordance with the disclosure, a catheteris introduced into the great cardiac vein, and a guidewire or otherpenetrating device (such as a needle, radiofrequency energy ablationdevice or laser ablation device) into a basal blood vessel such as thefirst septal coronary vein. From there the penetrating device directlytraverses under imaging guidance the septal myocardium or annulusfibrosis and reenters the right ventricle or right atrium. The guidewireis then retrieved using, for example, a snare catheter as disclosedherein. The snare catheter is then collapsed to draw the guidewire intoa body of the target catheter, and the guidewire is percutaneouslywithdrawn from the patient, resulting in both ends of the guidewirebeing exposed. The distal end of the implant is then crimped onto theproximal end of the guidewire, and the implant is advanced into the bodyuntil the bridge portion of the implant straddles a coronary artery,such as the left circumflex (“LCx”) artery. The location of the LCxartery can be identified, for example, by radiocontrast angiography orby fusion of prior computed tomography angiography and live X-ray orusing intravascular ultrasound. In an alternative approach, coronaryveins are entered in the other direction from the right atrium or rightventricle under imaging guidance into a branch of the coronary sinus.

At this point, the proximal end of the guidewire and the crimp attachingthe guidewire to the distal end of the implant are preferablyexternalized with respect to the patient's body, as well as the proximalend of the implant. The distal and proximal delivery tubes are thenpreferably removed, leaving behind the implant, wherein the sheathmaterial is long enough to extend out of the patient. A lock can then bethreaded over both proximal and distal sheath portions of the implantthat respectively contact the bridge portion using a lock deliverycatheter, and the lock can be advanced into the patient's heart. Tensioncan be imposed in the sheath of the implant to achieve the desiredanatomical change. Tension is preferably applied to the proximal anddistal sheath portions under imaging guidance until the desired degreeof mitral annular circumferential reduction is accomplished, or untilthe mitral valve regurgitation is reduced, or until other deleteriousendpoints are achieved such as mitral valve inflow obstruction. The lockcan be locked via manipulation of the lock delivery catheter, which thenin turn can be removed, and a cutting catheter can be advanced over theproximal and distal sheath portions of the implant. The sheath portionsare preferably internal to the lock and lock catheter. Excess sheath canbe removed using the cutting catheter as disclosed herein, and thecutting catheter can both be removed from the patient, completing theprocedure.

In accordance with further aspects, the disclosure provides animplantable pacing system configured and arranged to circumnavigate aloop path in a heart. The system includes an elongate inner tetherhaving a proximal end and a distal end, an outer sheath materialsurrounding the elongate inner tether having a proximal end and a distalend, at least one electrical conductor disposed along or within at leastone of the elongate inner tether and the outer sheath, a cardiac pacingcontroller including a power source, a pulse generator, and controlcircuitry operably coupled to the at least one electrical conductor, atleast one cardiac pacing electrode configured and arranged to beimplanted in cardiac tissue, the at least one cardiac pacing electrodebeing electrically coupled to the cardiac pacing controller by way ofthe at least one electrical conductor, and a lock securing the proximalend and distal end of the outer sheath material.

In some implementations, the lock can be coupled to the cardiac pacingcontroller. The at least one electrical conductor is disposed at leastpartially within the elongate inner tether. If desired, the lock caninclude cardiac pacing lead routed therethrough. Electricalcommunication can be established with the cardiac pacing lead byengaging a portion of the lock. In some implementations, the pacingsystem can further include at least one lumen along a length of theouter sheath for receiving a pacing lead, wherein the pacing system canbe slid along the pacing lead into the coronary sinus. The at least onelumen can be configured to direct the pacing lead toward the cardiacpacing controller. In some embodiments, the system can include aprotective bridge for spanning the LCx artery when in the coronary sinusnear the septal wall as described elsewhere herein. In some embodiments,at least a portion of the cardiac pacing controller can be disposedwithin the outer sheath.

The pacing system can further include an electrical battery that is atleast partially disposed within the outer sheath. The pacing system canfurther include a circuit board that is at least partially disposedwithin the outer sheath. The pacing system can further includecommunications circuitry that is at least partially disposed within theouter sheath.

If desired, the pacing system can further include at least one sensorcircuit that is at least partially disposed within the outer sheath, theat least one sensor module including at least one sensor (e.g., sensingcircuitry) for sensing at least one biological parameter. For example,the at least one sensor circuit/module can include at least one pressuresensor for detecting blood pressure, or at least one of a chemicalsensor, a distance sensor, a sensor having circuitry to detect electrophysiological data, a movement sensor, and a location sensor.

In some implementations, the at least one electrical conductor canterminate at the lock. If desired, the system can further include atleast one pacing lead (and/or electrical sensor for sensing cardiacelectrical signals) formed into a surface of the outer sheath. The atleast one pacing lead can be configured and arranged to interface withthe Right Atrium. If desired, a further pacing lead can be configuredand arranged to interface with the Right Ventricle, or a cardiac veinsuch as the septal vein. If desired, the controller can be configuredand arranged to provide at least one of pacing, defibrillation,measurement and control.

In some implementations of the pacing system the inner elongate tethercan include a loop antenna that conducts signals to and from thecontroller. In further implementations, the pacing system (or othersystem) can further include a reservoir for containing a beneficialagent coupled to a dispenser controlled by the controller. For example,the beneficial agent can include a medication, a gene therapy material,and/or living cells for seeding at least one location of the heart thatis damaged.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and are intended toprovide further explanation of the embodiments disclosed herein.

The accompanying drawings, which are incorporated in and constitute partof this specification, are included to illustrate and provide a furtherunderstanding of the method and system of the disclosure. Together withthe description, the drawings serve to explain the principles of thedisclosed embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, aspects, features, and advantages ofexemplary embodiments will become more apparent and may be betterunderstood by referring to the following description taken inconjunction with the accompanying drawings, in which:

FIGS. 1A-1C illustrate aspects of cardiac pacing in accordance with thepresent disclosure.

FIG. 2 is a schematic view showing an exemplary coronary protectivedevice in position during a cerclage annuloplasty procedure.

FIG. 3A is a left lateral external perspective view of the heart showingthe lateral coronary artery branching from the ascending aorta, thebranch of the lateral circumflex artery, and the great cardiac vein.

FIG. 3B is an enlarged view of a section of the arteries showing thecoronary sinus crossing superficial to the left circumflex coronaryartery at the level of the great cardiac vein.

FIG. 3C is a view similar to FIG. 3B but showing placement of a ligature(for example, and without limitation, a wire or suture) duringannuloplasty without the protective device in place. When the ligatureis tightened during the annuloplasty procedure, pressure is exerted onthe branch of the coronary artery, restricting blood flow and myocardialperfusion.

FIG. 3D is an enlarged view of this same structure showing placement ofthe protective device over the ligature within the coronary sinussuperficial to the coronary artery.

FIG. 4A is a schematic view of a portion of an implant in accordancewith the present disclosure.

FIG. 4B is a side view of an illustrative protection element inaccordance with the present disclosure.

FIG. 4C is a cross-sectional schematic view of an illustrative implantin accordance with the present disclosure.

FIG. 4D is a view of an inner tether suitable for use in the implant ofFIG. 4C.

FIGS. 4E-4F are views of a further embodiment of an implant inaccordance with the present disclosure.

FIGS. 5A-5E illustrate various aspects of a crimp in accordance with thepresent disclosure used to connect a distal end of an illustrativeimplant to a proximal end of a guide wire that has been directed througha patient's vasculature.

FIG. 6A is a schematic diagram of an embodiment of a snare catheter inaccordance with the present disclosure.

FIGS. 6B-6C are illustrations of target wires for use with the snarecatheter of FIG. 6A.

FIG. 7A is a schematic top view of a human heart, taken at the level ofthe atrioventricular valves, showing in dashed lines two alternativetrajectories of the cerclage annuloplasty ligature around the mitralvalve.

FIG. 7B is a front perspective view of the heart with portions of themyocardial wall broken away to show the cerclage annuloplastytrajectories of FIG. 7A.

FIG. 8 is a rear perspective view of the heart showing the tilted planeof the coronary sinus cerclage annuloplasty. The drawing schematicallyillustrates a smaller traditional surgical mitral valve annuloplastyring over the mitral valve annular plane and the larger coronary arterycerclage in a plane that is tilted to the mitral plane so as toencompass the left ventricular outflow tract.

FIG. 9 is a schematic cross-sectional view of the mitral valve region ofa heart wherein a prosthetic heart valve is positioned within the mitralvalve region and applies an outward expansion force and a mitralcerclage implant in accordance with the disclosure is positioned aroundthe mitral valve region and applies an inward force, and a coronaryprotection device in accordance with the disclosure is positioned alongthe mitral cerclage device to protect the coronary artery from beingcompressed.

FIG. 10 is a cross-sectional view of a heart with a mitral cerclagedevice being delivered through the coronary sinus and around the mitralvalve.

FIGS. 11A and 11B illustrate aspects of a lock delivery system inaccordance with the disclosure.

FIGS. 12A-12D illustrate aspects of a first embodiment of a limb ofadjustable length for attachment to a lock and lock delivery system inaccordance with the present disclosure.

FIGS. 12E-12H illustrate aspects of a first embodiment of a limb ofadjustable length for attachment to a lock and lock delivery system inaccordance with the present disclosure.

FIGS. 13A-13C illustrate deployment of the lock on the exemplarycerclage device in an animal.

FIGS. 14A-14I illustrate aspects of a cutting instrument in accordancewith the disclosure.

FIGS. 15A-15E illustrate aspects of a further embodiment of a lock andlock delivery system in accordance with the present disclosure.

FIGS. 16A-16D illustrate a particular embodiment of a lock in accordancewith the present disclosure.

FIG. 17 illustrates a further embodiment of a lock in accordance withthe present disclosure having at least one limbs with interchangeableends of different lengths, wherein the ends are also of adjustablelength.

FIG. 18 illustrates an embodiment of a system for delivering cardiacpacing and/or a beneficial agent in accordance with the presentdisclosure.

FIG. 19 illustrates a straightening, or disentangling catheter inaccordance with the present disclosure.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS I. Explanation of Terms

Unless otherwise noted, technical terms are used according toconventional usage. In order to facilitate review of the variousembodiments of the disclosure, the following explanation of terms isprovided:

“Annuloplasty element” refers to a device that induces reshaping of anannulus of the heart to repair valvular insufficiency. Such devicesinclude those that are placed in the coronary sinus and exert theiraction by compressive forces on the annulus, for example by expansion ofa resilient annuloplasty element, or placement of the annuloplastyelement under tension, as in cerclage annuloplasty.

The term “comprises” means “includes without limitation.” Thus,“comprising a guiding catheter and a guide wire” means “including aguiding catheter and a guide wire,” without excluding additionalelements.

The term “guide wire” refers to a simple guide wire, a stiffened guidewire, or a steerable guide-wire catheter that is capable of puncturingand/or penetrating tissue. The guide-wire also can deliver energy toaugment its ability to penetrate tissue, for example by puncturing it,delivering radiofrequency ablative energy or by delivering laserablative energy.

These are examples of a “penetrating device,” which is a device capableof penetrating heart tissue, such as the myocardium.

As used herein, the term “ligature” is meant to encompass any suitabletensioning material and is not limited to only suture material. The term“tensioning material” or “ligature” includes sutures and annuloplastywires.

A “mitral valve cerclage annuloplasty” refers to an annuloplastyprocedure in which a tensioning element is placed through at least aportion (and preferably all) of the coronary sinus so that thecircumferential tension is delivered around the mitral valve annulus andso that a tensioning element can be placed under selective degrees oftension to perform the annuloplasty. An example of cerclage annuloplastyis disclosed in co-pending prior application Ser. No. 11/127,112 (U.S.Patent Publication No. 2005/0216039), and the disclosure of thedescription of that technique is incorporated herein by reference forany purpose whatsoever. However, the mitral valve cerclage annuloplastytechnique also includes other cerclage trajectories, such as thosedisclosed herein, including a trajectory through a proximal coronaryseptal perforator vein and myocardium or annulus fibrosis interposingbetween that vein and the right ventricle or right atrium to createcircumferential cerclage annuloplasty tension.

The protective (or protection) device disclosed herein can be made of an“MRI-compatible” material. Such materials are safe to use in the bodyduring magnetic resonance imaging of the body, and do not substantiallyaffect imaging quality of the MRI. An “MRI-safe” material is one thatdoes not add substantial risk to a human or equipment by placing it inthe magnetic field of an MRI environment. Examples of MRI-compatiblematerials are non-ferrous materials, such as ceramics, plastics andnonmagnetic composite materials. Austenitic stainless steels (of the 300series) are neither ferromagnetic nor paramagnetic and therefore areMRI-compatible. Titanium and aluminum are MRI-compatible, even thoughthey are not ideally paramagnetic. Particularly disclosed MRI-compatiblematerials of which the protective device may be made include nitinol,MP35N and cobalt-chromium alloys.

“Tensioning material” is any material suitable to perform a coronarysinus mitral valve cerclage annuloplasty, in which an encirclingmaterial is placed under tension to remodel the mitral valve annulus.Examples of suitable tensioning materials are preferably a sheathmaterial (e.g., made from a woven polymeric material) as describedherein.

Unless otherwise explained, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this disclosure belongs. The singular terms“a”, “an”, and “the” include plural referents unless context clearlyindicates otherwise. The term “or” refers to a single element of statedalternative elements or a combination of two or more elements, unlesscontext clearly indicates otherwise. For example, the phrase “rtMRI orechocardiography” refers to real-time MRI (rtMRI), echoradiography, orboth rtMRI and echocardiography. Although methods and materials similaror equivalent to those described herein can be used in the practice ortesting of the present disclosure, suitable methods and materials aredescribed below. In case of conflict, the present specification,including terms, will control. In addition, the materials, methods, andexamples are illustrative only and not intended to be limiting.

II. Protection Devices to Protect Coronary Arteries

Coronary sinus mitral valve cerclage annuloplasty is an example of apercutaneous mitral valve repair procedure for which the disclosedprotective device can be used. Although the device and methods of itsuse are broadly applicable to any prosthetic annuloplasty element placedin the coronary sinus, the methods will be described in connection withthe particular example of cerclage annuloplasty. This specific exampleshould not be construed to limit the procedure to use with cerclageannuloplasty, but only to illustrate its use in a particular embodiment.

Cerclage annuloplasty percutaneous repair carries a lower risk ormorbidity than conventional mitral valve surgery, and thus can be usedin patients who have less severe or more severe valvular dysfunction.Placing cerclage tethers, or ligatures, at least partially through thecoronary sinus takes advantage of the proximity of the coronary sinus tothe mitral valve annulus, and of the ready catheter access to thecoronary sinus and tributary veins. These approaches also have limitingdrawbacks, however, in that compression of nearby coronary arterybranches is a serious risk in a majority of human subjects. The coronarysinus usually runs superficial to the circumflex coronary artery and itsmarginal branches near the great cardiac vein, and therefore trans-sinusannuloplasty can transmit pressure sufficient to constrict or occludethe coronary artery or its branches. Devices and methods that preventthis compression of the coronary artery, such as those disclosed herein,can dramatically increase the safety and efficacy of trans-sinus mitralcerclage annuloplasty.

An exemplary transcatheter-mitral-valve-cerclage annuloplasty involvesthe introduction of a tensioning material or device around the mitralvalve annulus using a guiding catheter and a secondary catheter, such asa steerable microcatheter directing coaxial guide wires or canalizationcatheter. Access to the area around the mitral-valve annulus can beaccomplished using a variety of percutaneous approaches, includingaccess from and through the coronary sinus. In particular embodiments, atensioning material that constitutes a portion of an implant is appliedaround the mitral-valve annulus along a pathway that, in certainembodiments, includes an extra-anatomic portion. For example (andwithout limitation), the tensioning material can traverse a regionbetween the anterobasal-most portion of the coronary sinus and thecoronary-sinus ostium. As another non-limiting example, such tensioningmaterial can be applied across the atrial aspect of the mitral valvefrom the posterolateral aspect to the anterior aspect of the coronarysinus, or from the septal aspect to the lateral aspect of themitral-valve annulus. This procedure reduces the mitral annularcross-sectional area and septal-lateral wall separation, therebyrestoring a line of coaptation of the mitral valve.

Because it has been found that mitral annuloplasty via the coronarysinus unintentionally transmits pressure sufficient to constrict orocclude the underlying coronary artery, the devices disclosed hereinhave been developed to increase the safety and efficacy of theprocedure. The disclosed improved devices and related methods protect anunderlying vessel from compression during mitral annuloplasty in which acerclage ligature extends at least partially through the coronary sinusover a coronary artery. As discussed in U.S. patent application Ser. No.15/056,599, filed Feb. 29, 2016, a coronary protection element isdisclosed for use with a cerclage device. However, the presentlydisclosed embodiments provide significant improvements over thatdisclosure.

FIG. 2 schematically illustrates the use of implant 400 using aprotection device 420 in a mitral valve cerclage annuloplasty procedure.FIG. 2 depicts sheath material 450 used as a tensioning element (in apreferred embodiment, braided suture material) extending through aportion of the coronary sinus 250 over a circumflex coronary artery 252.FIG. 2 shows implant 400 positioned within coronary sinus 250 withprotection element 420 extending over coronary artery 252, and proximaland distal portions 428, 429 being located on either side of coronaryartery 252. As tension is placed on the tether portion 450 of implant400, the proximal and distal portions 428, 429 are held in place oneither side of coronary artery 252 and transmit compressive forces tothe wall of coronary sinus 250 instead of on to underlying coronaryartery (LCx) 252.

FIGS. 3A, 3B, 3C and 3D provide an alternative view of the function ofcerclage annuloplasty protection device 400.

FIG. 3A shows the external anatomy of the heart, with coronary sinus 250extending over a circumflex branch 252 of a left coronary artery 254.FIG. 3B shows an enlarged view of the overlapping relationship ofcoronary sinus 250 to coronary artery 252. FIG. 3C illustrates hollowtether 450 placed under tension during cerclage annuloplasty which iscompressing underlying coronary artery 252 and interfering withmyocardial perfusion. FIG. 3D shows hollow tether 450 extending throughprotection device 420 which is inhibiting the application of compressiveforce to coronary artery 252 which therefore remains patent and able tonormally perfuse myocardial tissue.

It will be appreciated that the bridge/protection device (e.g., 400) canassume a variety of shapes and configurations that support the hollowtether material 450 away from an underlying coronary artery (e.g., LCx).The protection device/bridge 420 can be pre-shaped to the desiredconfiguration, or it can be made of a memory alloy material that isgenerally linear when being advanced through the vasculature but assumesthe desired protection device shape once it is fully deployed. Thebridge 420 can have curvature in three dimensions, as desired, toconform to a unique anatomy of an individual.

FIGS. 4A-4D illustrate an embodiment of an implant 400 that includes aprotection bridge 420. A distal end of the implant 400 is connected to acrimp 570 to facilitate its delivery as set forth below. A distaldelivery tube 440 is slipped over a distal portion of a sheath 450 thathouses various components of the implant 400. The crimp 570 is crimpedat its proximal end around the distal end of the sheath and componentsinside the sheath at the distal end of the implant 400.

As illustrated in FIGS. 4A-4D, the implant 400 includes an arch-shapedprotection element 420. A hollow tether 410, such as a small diameterbraided polyester suture, is laid on top of the protective arch 420, andsecured in place, for example, by suture loops (not shown), or one ormore pieces of shrink tubing (not shown). In one implementation, a pieceof shrink tubing is slid over tether 410 and protective arch 420, andshrunk in place, holding tether 410 in place on the upper surface of thearch 420 from end to end. If desired, this shrink tubing can extendbeyond the ends of the protection element 400 to act as a strain reliefto provide a gentler transition in stiffness at the ends of the element420. Also, if desired, additional or alternative strain reliefs 430 canalso be provided at the ends of the protective element 420, alsosurrounding the tether 410. A sheath 450, such as a larger diameterbraided suture, is then fit over the assembly of elements 410, 420, and430, for example. Sheath 450 narrows in the regions where the protectiveelement 420 is not present. A distal delivery tube 440 is slid over thedistal region of the sheath 450, and a proximal delivery tube 470 isslid over the proximal region of the sheath 450, and if desired, crimpedin place at the distal and proximal ends of the implant, respectively.

FIG. 4B illustrates an embodiment of a protection device 420, or arch,that has a significantly elongated proximal portion 428 that forms a“landing zone”, or stiff, stable structure when implanted within thecoronary sinus. This landing zone can then serve as a location forimplanting a replacement valve after the transcatheter annuloplastyprocedure has been completed. Specifically, having a relatively rigidsurface within the heart provided by the landing zone created byelongated proximal portion 428 facilitates anchoring of such areplacement valve to the native tissue. The proximal portion 428, ifprovided, can thus have any suitable length between, for example, 3 and80 mm, and in any desired increment of 1 mm therebetween. The distalportion 429, if provided, can have any suitable length between 0.5 mmand about 10 mm, and in any desired increment of 0.5 mm therebetween.

The protection element 420 can be made from rolled wire that isradiopaque, such as 0.020 inch by 0.070 inch Ni Ti alloy shape memorywire, but it will be appreciated that other materials can be used ofsimilar or differing dimension. Being made from a shape memory materialallows the bridge 420 to be deformed (for example toward a linearconfiguration) that is adaptable to introduction through the vascularsystem. However, the shape memory material returns to the archedconfiguration shown in the drawings after the device is deployed.

The arch 420 may have a round cross section or rectangular cross sectionhaving a diameter, or respective height and width between about 0.010inches to about 0.080 inches and in any desired increment of 0.001inches between those values. As illustrated, the ends of the protectionelement 420 are preferably rounded so as to not cause trauma to the wallof the coronary sinus as it is advanced. The protection device 420preferably has an arcuate, or semi-circular shape of sufficient radiusto extend closely over an underlying coronary artery (e.g., the LCx) toinhibit the transmission of compressive forces from the tension elementto the underlying artery. The compressive forces are instead distributedon and along the protection device to protect the artery fromcompression that impairs myocardial perfusion. Protection element endportions 428, 429 effectively form “feet” that can rest against a wallof the coronary sinus while straddling a coronary artery to retainprotection device 420 in position over the left circumflex artery andbear and distribute the compressive forces that are applied by thesheath 450 when the under tension after the delivery tubes 440, 470 areremoved.

The embodiment of FIG. 4C preferably has a central arch bridging alinear distance at its base of from about 0.4 inches to about 0.7inches, for instance, in any desired increment of 0.01 inchestherebetween. The illustrated central arch has a height h from about0.10 inches to about 0.20 inches high, for instance, in any desiredincrement of 0.01 inches therebetween.

The proximal and distal portions of the exterior sheath and the deliverytubes 440, 470 are preferably coated with a lubricious hydrophobic orhydrophilic material, such as PTFE, PVDF, other suitable fluoropolymeror PVP, for example.

As illustrated in FIG. 4D, the inner tether 410 can be composed of aplurality of sub-components. The illustrated embodiment of inner tether410 can be composed of an innermost metallic, radiopaque wire 410 a(e.g., platinum), surrounded by a heat shrunk tubing 410 b (e.g., PTFE,PET). These nested components can then accordingly be housed withinbraided suture 410 c. Preferably, the lengths of components 410 a, 410b, 410 c are coextensive with sheath 450 and crimped to sheath 450 atthe proximal and distal ends of the implant 400.

Preferably, the inner tether is 410 radiopaque along its entire lengthto enhance visualization thereof during and after installation. Whileradiopacity of inner tether 410 can be enhanced by the presence of ametallic (e.g., platinum) wire, the wire, or filament, can be formedfrom a tungsten loaded polymer, a tantalum loaded polymer, and/or thebraided suture material 410 c can be used that is impregnated in onemanner or another (e.g., by incorporation into the underlying polymer,or into the woven material) with one or more of bismuth, tungsten,tantalum, barium sulfate, and the like.

The delivery tubes 440, 470 are disposed over the sheath 450, and mayabut, or be located near, the proximal and distal ends of the protectionbridge 420. The removable delivery tubes are assembled over thecontinuous outer tether 450 on each side, running from the protectionbridge to the exchange crimp (as illustrated in FIG. 4A) to aid inexchanging out the guide wire for the cerclage implant. Alternatively,they can be routed underneath the outer sheath 450. The removabledelivery tubes can be made from polymeric material, for example, such asPEEK, HDPE, or the like, as desired. When the implant is in place, theremovable delivery tubes can be removed by pulling them out. The sheath50 surrounding the structure can, in turn, include a lubricious coatingalong at least a portion of its length or all of its length, such as ahydrophobic coating (e.g., PTFE, PVDF) or a hydrophilic coating (e.g.,PVP). This can be provided, for example, in the form of one or moreadditional layers or adjacent and/or overlapping tubes of PTFE shrinktubing. The overlap regions can act as a strain relief to help provideregions of transitioning stiffness. The shrink tubing can be amulti-layer co-extrusion as described elsewhere herein that can includean intermediate braided layer formed from polymeric or metallicmaterial, and may include radiopaque material.

In some implementations, sheath 450 can be made from a 1-2 mm ultra highmolecular weight polyethylene (“UHMWPE”) coreless round braid from DSM,Dyneema or Teleflex. In some embodiments, the tether/sheath 450 can beloaded with at least 20% bismuth by weight to enhance radiopacity. Forexample, the sheath may be loaded with between about 20 and about 70%bismuth or barium sulfate, or to any degree therebetween in incrementsof about 1% by weight. Additionally or alternatively, additional oralternative radiopaque materials can be incorporated into the sheathmaterial, such as tungsten, tantalum, and barium sulfate. Thesematerials can be incorporated, for example, as drawn metallic (e.g.,platinum, or other radiopaque material) wires incorporated into thebraiding, such as by weaving, or by directing the drawn wire along acentral channel defined within the tether.

FIGS. 5A-5E depict various views of a crimp 570 that provides atransition region from a proximal end 502 of a guidewire to a distal endof the implant 400. A second crimp at the proximal end of the implant400, if provided, can provide an alternative or additional structuralattachment location for affixing the proximal end of the sheath 450 to aproximal end of the inner tether 410. As illustrated, the crimp 570includes an external proximal tapering generally conical surface, anexternal distal tapering generally conical surface and two intermediatetapering external conical surfaces. The distal end of the crimp issmaller in diameter than the proximal end of the crimp 570 to define arelatively large proximal bore for receiving the distal end of theimplant 400 housed within and including distal end of sheath 450, and arelatively narrow, intersecting distal bore that is sized to receive theproximal end 502 of a guidewire. The crimp 570 is preferably made from adeformable metallic material that is initially affixed to the distal endof the implant 400. Once the guidewire is introduced and has beenproperly routed through the heart and out of the body (discussed infurther detail below), the crimp 570 of implant 400 is then crimped ontothe guidewire (e.g., with a hand crimper), and the implant 400,including the proximal and distal delivery tubes, protection element 420and sheath 450 are advanced through the vasculature until the protectionelement straddles the LCx artery. It will be appreciated that theprotection element 420 can be omitted from the implant, and, forexample, replaced with a relatively straight structural element (or nostiff element at all) for patients having anatomy that does not requirethe arched protection element.

FIGS. 4E and 4F illustrate a further embodiment of an implant 400′ inaccordance with the present disclosure. FIG. 4E illustrates a distal andcentral portion of implant 400′. Implant 400′ includes an innermost corewire (e.g., of platinum) 410 a′ that is preferably housed within anelongate Pebax tube 410 b′. The assembly of components 410 a′, 410 b′are then introduced into a tubular (e.g., 0.5 mm) braided suture 410 c′.This collection of components is then introduced into a shorter tube480′, preferably also of Pebax or other suitable thermoplastic material.Tube 480′ is preferably only several inches long and sufficient to spanthe full length of protective bridge 420′. Components 410 a′, 410 b′,410 c′ and 480′ are then heat shrunk in a heating operation. The heatingoperation causes the Pebax material to melt in between the fibers of thebraided suture 410′, enhancing its stiffness in the region of theprotective bridge 420′. The heat fused assembly of components 410 a′,410 b′, 410 c′ and 480′ are then laid over the upper surface of bridge420′, and then introduced into a further (e.g., 1 mm diameter) braidedpolymeric suture 450′. The suture 450 holds the assembly of components410 a′, 410 b′, 410 c′ and 480′ in place on the upper surface of bridge420′. Next, an outer tubular layer 490′ of Pebax or other suitablethermoplastic material is fitted over the portion of the outer sheath450′ that straddles the bridge 420′. This collection of components isthen heat shrunk again to cause the polymeric material of components480′ and 490′ to fuse into the fibers of braided sheath 450′, furtherenhancing stiffness, and also providing a smooth surface with superiorstress transition aspects along the length of the implant 400′. Innerradiopaque wire 410 a′ preferably does not traverse the entire length ofthe implant, but instead preferably occupies a central region that isbetween about 100 cm and 200 cm long (e.g., about 170 cm long) withroughly equal lengths on either side of bridge 420′.

As further illustrated in FIG. 4E, a distal delivery tube 440′ is alsopresented, and also preferably made from a thermoplastic polymer(preferably thermoplastic elastomer “TPE”) such as Pebax. Asillustrated, delivery tube 440′ includes a flared proximal end suitablefor abutting or even partially overlapping the distal end of bridge420′. A proximal delivery tube 470′ (not specifically illustrated) cansimilarly be provided with a distal flare that similarly abuts oroverlaps the proximal end of the bridge 420′.

FIG. 4F shows a distal region of implant 400′ showing how it is affixedto a distal crimp 570′ in cross-section. Distal crimp 570′ includes adistal passage for receiving a guidewire (not shown) and a proximalpassage for receiving a plurality of nested tubular components. Theinnermost component illustrated in FIG. 4F includes Pebax tube 410 b′which is nested inside braided suture 410 c′. Core wire 410 a′ does notextend all the way to the crimp in this embodiment, although it could ifdesired. Component 410 c′ is disposed within outer sheath, or braidedsuture 450′. The distal end of suture 450′ is in turn disposed within ashort (e.g., 2-3 cm) section 572′ of polymeric tube, such as Pebax. Thedistal end of tub 572′ is fit into a cylindrical opening in the proximalface of crimp 570′. Outer delivery tube 440 is then slid over anexterior proximal portion of crimp 570′, which may be recessed. Proximalportion of crimp 570′ includes a plurality of holes, or windows 574′,formed therethrough. Once the components are assembled, the assembly isheat shrunk to cause the polymers in the distal tip of delivery tube440′ to fuse with tube 572′ through windows 574′, thereby affixing crimp570′ to implant 400′. The distal end of tube 440′ may initially beoutwardly flared to help with initially fitting the components into oronto crimp 570′. While not shown, the proximal end of the implant 400′can be constructed similarly and fused without a crimp, for example, byheat shrinking the proximal end of the proximal delivery tube 470′ tothe interior components.

The disclosure also provides a version of implant 400′ that does notinclude a protective bridge. The construction this embodiment is thesame as implant 400′, except that in the central region where the bridge420′ would otherwise be, the bridge 420′ is not present, and tube 480′is not included. Instead, the assembly of components 410 a′, 410 b′ and410 c′ are heat fused, and introduced into outer sheath 450′. In orderto indicate the location of the center of the implant 400′, a markerband is slid to that location over sheath 450′ and held in place bysliding another polymeric tube, preferably of Pebax, over the marker,and heat shrinking it into place. If desired, a further piece of heatshrink tubing can be shrunk over the marker that may also be at leastpartly radiopaque to both enhance radiopacity but also to increase thethickness at the center of the implant to prevent it from being pulledthrough the lock as a safety feature during implantation.

III. Percutaneous Mitral Valve Cerclage Annuloplasty

A. Mitral Regurgitation

Regurgitation (leakage) of the mitral valve or tricuspid valve canresult from many different causes, such as ischemic heart disease,myocardial infarction, acquired or inherited cardiomyopathy, congenitaldefect, traumatic injury, infectious disease, and various forms of heartdisease. Primary heart muscle disease can cause valvular regurgitationthrough dilation, resulting in expansion of the valvular annulus leadingto malcoaptation of the valve leaflets through overstretching,degeneration, or rupture of the papillary muscle apparatus, or throughdysfunction or malpositioning of the papillary muscles. Thisregurgitation can cause heart rhythm abnormalities such as atrialfibrillation, which itself can cause inexorable deterioration in heartmuscle function. Such deterioration can be associated with functionalimpairment, congestive heart failure and significant pain, suffering,lessening of the quality of life, or even premature death.

A less dangerous, minimally invasive procedure, such as percutaneousannuloplasty, permits more patients to undergo mechanical treatment ofvalvular regurgitation.

B. Percutaneous Cerclage Annuloplasty

Because the risks and complications of surgery are reduced (comparedwith open-heart surgery), catheter-based heart-valve procedures aresuitable for a broader population of patients. Disclosed herein areimproved devices and methods for catheter-based valve repair that can beused to repair damaged or malfunctioning cardiac valves, for instance,by re-apposing valve leaflets by percutaneous-cerclage annuloplasty(reconstruction or augmentation of the ring or annulus of a defectivecardiac valve). In some instances, percutaneous cerclage annuloplasty isused to deliver circumferential or radial tensioning devices. Examplesof some of these procedures are described in detail in WO2004/045378 andUS 2005/0216039, which are incorporated herein by reference in theirentireties for any purpose whatsoever.

In general, the system used to carry out an annuloplasty procedure caninclude a guiding catheter (GC), such as a preformed transjugularballoon-tipped guiding catheter which is introduced into the coronary(venous) sinus. A retrograde coronary radiocontrast venogram pressurizesand visualizes the great cardiac vein and septal perforator veins. Ahigh performance guidewire designed for coronary artery recanalizationmay be steered using a deflectable microcatheter, for example, into thegreat cardiac vein and thereafter into a basal septal perforator vein.

In general, an annuloplasty procedure also can include using an imagingsystem to image the internal bodily tissues, organs, structures,cavities, and spaces of the subject being treated. For example,transmitter or receiver coils can be used to facilitate active-devicenavigation using an imaging system, such as magnetic-resonance imaging(MRI). This imaging can generally be conducted along arbitrary orpredetermined planes using various imaging methods based on X-raytechnologies, X-ray fluoroscopy, MRI, electromagnetic-positronnavigation, video technologies (such as endoscopy, arthroscopy, and thelike), ultrasound, and other such technologies. In some embodiments,real-time MRI (rtMRI), intracardiac ultrasound, or electromagneticguidance is employed. A particularly useful adjunct in cerclageannuloplasty is XFM, in which X-Ray is used with MRI to targetmyocardial structures, for example to help guide the annuloplasty wirein its trajectory through the structures of the heart. The XFM techniqueis disclosed, for example, in de Silva et al., Circulation 114:2342-2350(2006). The guiding catheter enables percutaneous access into asubject's body, for example, percutaneous access to the heart, such as achamber of the heart through an arm, neck, or leg vein. In someembodiments, the guiding catheter is designed for access to theventricle and/or atrium of the heart. The guiding catheter permitsintroduction of one or more secondary catheters, including avalve-manipulation catheter or microcatheter or canalization-needlecatheter, for example. The secondary catheter (or catheters) is used totreat, affect, or manipulate an organ, tissue, or structure of interestin the subject's body, such as the heart or particular structures withinthe heart. If the guiding catheter is used for percutaneous (or other)access to the heart, the guiding catheter permits introduction of one ormore secondary catheters, such as a valve-manipulation catheter, intothe heart while maintaining hemostasis. The secondary catheters may becoaxial or adjacent to each other, or may be introduced from multiplepoints of access outside the body.

Guiding catheters are available in different shapes to suit theappropriate component of the mitral-valve-repair procedure. For example,guiding catheter shapes can be provided to suit different coronarysinuses with different radii of curvature, to suit different coronaryveins, transaortic as well as transseptal access routes, or to suitatria and ventricles of different calibers. All such shapes can beaccommodated with appropriate primary, secondary, and tertiary curves.Examples of catheter configurations suitable to perform percutaneoustransvascular mitral valve annuloplasty are known in the art and aredescribed in detail in U.S. Patent Publication No. 2005/0216039, whichis incorporated by reference herein in its entirety for any purposewhatsoever.

Although any available approach to the coronary sinus may be used, avenous approach is preferred, for example through the jugular vein. Asyet another example, the guiding catheter can be introduced into a vein,such as the femoral or jugular vein, and guided through the inferior orsuperior vena cava into the right ventricle of the heart. Two examplesof trajectories for cerclage annuloplasty are shown in FIG. 7A and FIG.7B. The first trajectory (labeled a “simple” or “RV” trajectory) is onein which the annuloplasty wire enters the right atrium through thesuperior vena cava and is then introduced through the coronary ostiuminto the coronary sinus. The wire is advanced through the great cardiacvein into a basal blood vessel, such as a basal septal perforator vein.The wire then exits the septal perforator vein through myocardialinterstitium into the right ventricle, re-entering the right atriumalong the septal tricuspid valve commissure (at the intersection of theanterior cusp and the septal cusp).

The guidewire is then retrieved using, for example, a vascular snare.Any suitable instrument can be used to capture the distal end of theguidewire and withdraw it through the vasculature until it is exposedoutside the body. An illustrative preferred and improved snare system tofacilitate guidewire retrieval is also described further herein at FIGS.6A-6C.

For purposes of illustration, and not limitation, FIG. 6A illustrates anexemplary snare catheter 600 for capturing a guidewire, in accordancewith the disclosure. As illustrated in FIG. 6A, the snare catheter 600is defined by an elongate outer tubular member, or sheath, 601 thatslidably receives an intermediate tubular member 602 therein along itslength. The intermediate tubular member 602, in turn, includes a furtherelongate inner tubular member 604, such as a hypotube, slidably disposedtherein along its length. Relative axial displacement of tubular members602, 604 causes a wire snare basket 606 (e.g., a collapsible body) toexpand or collapse. Snare basket 606 is defined by a plurality ofpre-shaped wires, and has a proximal end 610 attached to the distal endof intermediate tubular member 602, and a distal end 612 attached to thedistal end of inner tubular member 604. As such, when the ends 612, 610are pulled away from each other by sliding tubular member 602 distallywith respect to tubular member 604, the pre-shaped wires of the basket606 are elongated and collapse radially inwardly, permitting basket 606to then be pulled proximally with respect to outer tubular member orsheath 601. Inner tubular member 604 is preferably a metallic member,such as a stainless steel or nickel-titanium alloy hypotube that definesa further lumen along its length that can accommodate a guidewiretherethrough. An atraumatic conically tapering atraumatic distal tip 605is preferably formed over the distal end of the inner tubular member 604and the distal end portion 612 of the snare basket 606.

Each of the wires comprising the snare basket 606 can be pre-shaped toexpand radially outward when the snare basket 106 is in a generallyexpanded state. For instance, as illustrated in FIG. 6A, each of thepre-shaped wires extends along a plane parallel to a longitudinal axisof the elongate core member 604, and extends radially outward in adirection orthogonal to the elongate core member 604 in the expandedstate. When the snare basket 606 is in the expanded state, the distancewith which each wire extends radially outward from the elongate coremember 604 is uniform and defined by the geometric shape of thepre-shaped wires. Further axial displacement of the distal end of theelongate intermediate tubular member 602 toward the distal end of theelongate core member causes the geometric shape of snare basket 606 tochange, via a change in the shape of each respective pre-shaped wire.For instance, displacement of intermediate tubular member 602 toward tip605 causes each of the plurality of pre-shaped wires to curve in adirection orthogonal to the plane parallel to the elongate core member(e.g., to curve radially outward). Conversely, displacement ofintermediate tubular member 602 in a direction opposite of tip 605causes each of the plurality of pre-shaped wires to contract radiallyinward toward elongate core member 604.

Thus, the snare catheter 600 can include elongate outer tubular member,or sheath, that slidably receives an intermediate tubular member thereinalong its length. The intermediate tubular member, in turn, includes afurther elongate inner tubular member, such as a hypotube, slidablydisposed therein along its length. Relative axial displacement oftubular members causes the snare basket filaments to expand or collapse.The snare “basket” as illustrated is formed from pre-shaped wires asillustrated in FIG. 6A. As described with regard to FIG. 6A, each of thepre-shaped wires of the snare basket has a proximal end attached to thedistal end of intermediate tubular member, and a distal end attached todistal end of the inner tubular member. As such, when the ends of theinner and intermediate tubular members are pulled away from each otherby relative sliding linear displacement, the pre-shaped wires of thebasket are elongated and collapse radially inwardly, permitting thebasket to then be pulled proximally with respect to the outer tubularmember or sheath and pulled into the distal end of the sheath. The innertubular member is preferably a metallic member, such as a stainlesssteel or nickel-titanium alloy hypotube that defines a further lumenalong its length that can accommodate a guidewire therethrough. Anatraumatic conically tapering atraumatic distal tip is preferably formedover the distal end of the inner tubular member (FIG. 6A) and the distalend portion of the snare basket. The distal tip can be overmolded overthe aforementioned components, or it may be pre-formed and adhered tothe system, such as with UV activated adhesive and the like.

Preferably, the distal tip defines a distal opening therethrough topermit a guidewire to pass therethrough after traversing the lumendefined inside inner tubular member. The distal tip of the device 600may be made from polymeric material such as PEBAX polymer, 35D Nylonmaterial, or any other suitable atraumatic material or other material,and may be provided with a lubricious hydrophobic or hydrophilic coatingas described elsewhere herein (e.g., PVP). Having the distal tip madefrom atraumatic material facilitates passage of snare catheter 600through tortuous vasculature including sharp turns to arrive in theright ventricle proximate the pulmonary valve to intercept the guidewirepassing through the septum wall after passing through the wall of thecoronary sinus, or passing the guidewire between the target septalperforator vein and the Right Ventricular Outflow Tract (RVOT). Theinner tubular member may traverse substantially the entire length of thedistal tip of the device 600, but preferably stops short of the distalend of tip to permit the tip to flex as it passes through vasculature.

Marker bands are preferably formed on the distal end portions of theinner, intermediate, and outer tubular members respectively. Also, asillustrated in FIGS. 6B-6C, if desired, an inner target filament, orwire 640, 650, may be provided having a two dimensional (FIG. 6B) orthree dimensional (FIG. 6C) looped geometry to facilitate capture of thedistal end of a guidewire passed through the wall of the septum into theregion of the right ventricle near the pulmonary valve. Each target wire640, 650 has a proximal end attached to the distal end of theintermediate tubular member and a distal end attached to the distal endof the inner tubular member of catheter 600. The target wire 640, 650further defines one or more wire loops therein laying in one or moreplanes. When the basket is elongated by virtue of longitudinallydisplacing the distal ends of relative longitudinal motion of theintermediate and inner tubular members, the target wire 640, 650similarly lengthens and the loop(s) collapse.

FIG. 6B illustrates a target wire 640 having a single loop. In eithercase, the wire 640 essentially lies in a single plane. FIG. 6Cillustrates a variation of the wire 650 wherein three loop-likeundulations are provided that mimic the loop of the wire 640 in FIG. 6B,but are formed in more than one plane using a single filament. Asdepicted, two of the undulations lay in the same plane, and areseparated by a third undulation that is in a second plane that is offsetby about ninety degrees with respect to the plane of the other twoundulations. The wires 640, 650 can be made from a variety of materials,such as nitinol or other material, and may be provided with a pluralityof marker bands 642, 652. In one embodiment, wires 640, 650 are formedfrom a composite wire, such as DFT® wire, available from Fort Waynemetals.

After snaring the guidewire and removing the distal end thereof from thepatient, the implant (e.g., 400) is exchanged for the guidewire bycrimping the implant onto the proximal end of the guidewire via crimp(e.g., 570). The implant (e.g., 400) can then be advanced along the pathof the guidewire as the guidewire is withdrawn from the patient untilthe distal end (e.g., 249) of the protection device or bridge (e.g.,420) is proximate the septum wall and the bridge is traversing the LCxartery. The location of the jeopardized coronary artery is confirmed,for example, by radiocontrast angiography. In an alternative approach,coronary veins are entered in the opposite direction from the rightatrium or right ventricle under imaging guidance into a branch of thecoronary sinus.

An alternative or “complex” right atrial cerclage trajectory shown inFIGS. 7A and 7B extends further posterior through the basal septalmyocardium into the right atrium near the coronary sinus. The wiretraverses deep tissue of the septum moving in a posterior direction andexits above the opening of the coronary sinus. The plane of theresulting cerclage annuloplasty is shown in FIG. 8C to be related to andin the plane of the coronary sinus 860 such that annuloplasty remainsuniquely feasible even if the coronary sinus is remote from the mitralvalve annuloplasty. As the figure indicates, the plane of cerclage 860enhances mitral valve coaptation, even when the coronary sinus isgeometrically remote from the mitral valve annulus, because it is“tilted” toward the left ventricular outflow tract. The illustratedangle α between the cerclage plane 860 and the plane of the mitral valveannulus 862 is therefore advantageous. Moreover, the illustratedtrajectories of the cerclage annuloplasty induces reciprocal mitralvalve coaptation and left ventricular outflow tract relaxation duringventricular systole.

The guide wire is dimensioned to operate with the guiding catheter andis usually longer than the guiding catheter. For example, a guide wireof about 100 to about 250 centimeters in length and about 0.1 to about 2mm in diameter can be used with the guiding catheter described above. Ifa secondary catheter, such as a tension delivery catheter, is intendedfor use with the guiding catheter, that secondary catheter also isdimensioned to operate with the guiding catheter and is usually longerthan the guiding catheter.

The guiding catheter can be made of any suitable material or combinationof materials that provide both the strength and flexibility suitable toresist collapse by external forces, such as forces imposed duringbending or twisting. Exemplary materials include, but are not limitedto: polymers, such as polyethylene or polyurethane; carbon fiber;ceramic; or metals, such as nitinol, platinum, titanium, tantalum,tungsten, stainless steel, copper, gold, cobalt-chromium alloy, ornickel. The guiding catheter optionally can be composed of or reinforcedwith fibers of metal, carbon fiber, glass, fiberglass, a rigid polymer,or other high-strength material. In particular embodiments, the guidingcatheter material is compatible with MRI, for example, braided nitinol,platinum, tungsten, gold, or carbon fiber. Additionally, the exteriorsurfaces of the guiding catheter can be coated with a hydrophobicmaterial or substance, such as Teflon® or other lubricous material, suchas a hydrophilic material (e.g., PVP) that aids with the insertion ofthe guiding catheter into the body of the subject and/or aids in themovement of the guiding catheter through the subject's body.

Additionally, the guiding catheter can include a deflectable tip, suchas a simple deflectable tip having a single degree of axial freedom.Exemplary (non-limiting) fixed-fulcrum andmoveable-fulcrum-deflectable-tip catheters are commercially available,such as the deflectable-tip catheters described in U.S. Pat. Nos.5,397,321; 5,487,757; 5,944,689; 5,928,191; 6,074,351; 6,198,974; and6,346,099, each of which being incorporated by reference herein in itsentirety for any purpose whatsoever. Thus, any suitable fixed-fulcrum ormoveable-fulcrum deflectable-tip catheter can be adapted for use as aguiding catheter disclosed herein. The guiding catheter also can includestructures or mechanisms for aiding in the rotation of the catheterabout its longitudinal axis.

The guiding catheter can include a guide collar, handgrip, handle, andother structures or devices at its proximal end that aid in operation ofthe guiding catheter. Various control mechanisms, including electrical,optical, or mechanical control mechanisms, can be attached to thecatheter via a guide collar. For example, a guide wire can be includedas a mechanical control mechanism. The guide collar can includeadditional operational features, such as a grip for aiding manualcontrol of the guiding catheter, markers indicating the orientation ofthe guiding catheter lumen or subdivided lumens, markers to gauge thedepth of guiding catheter advancement, instruments to measure guidingcatheter operation or physiological signs of the subject (for example, atemperature gauge or pressure monitor), or an injector control mechanismcoupled to the guiding catheter lumen for delivering a small, precisevolume of injectate. In some embodiments, the guide collar containsinstrumentation electrically coupled to metallic braiding within theguiding catheter, thus allowing the guiding catheter to simultaneouslybe used as a receiver coil for MRI.

A guide wire used with the system for guiding the guiding catheter intoand through a subject's body can be composed of any suitable material,or combination of materials, including the materials described above inrelation to the guiding catheter. Exemplary (non-limiting) guide wiresare composed of material having the strength and flexibility suitablefor use with the device, such as a strand of metal (for example,surgical stainless steel, nitinol, platinum, titanium, tungsten, copper,or nickel), carbon fiber, or a polymer, such as braided nylon.Particular (non-limiting) guide wires are composed of a strand ofNitinol or other flexible, kink-resistant material. The guiding catheteror guide wire can include an image-enhancing feature, structure,material, or apparatus, such as a radiopaque marker (for example, aplatinum or tantalum band around the circumference of the guide wire)adjacent its distal end. As another example, the guide wire can includeetchings or notches, or be coated with a sonoreflective material toenhance images obtained via intravascular, intracardiac,transesophogeal, or other ultrasound-imaging methods. As anotherexample, the guide wire can be coated with a T1-shortening orT2-shortening agent to facilitate passive visualization using MRI. Asyet another example, a fiber-optic secondary catheter can be insertedinto and through a secondary-catheter lumen of the guiding catheter toassist in visualizing the position of the guide wire within the subjectas a guide wire is deployed through the distal guide-wire lumen port. Insome embodiments, the guide wire and/or guiding catheter includes astructure, apparatus, or device at its distal tip useful for penetratingtissue, such as myocardial skeleton, muscle, or connective tissue. Forexample, the distal tip of the guide wire can be sharpened to a pointfor puncturing through tissue, or a secondary catheter having a coringmechanism or forceps at its distal tip can be used in conjunction withthe guiding catheter. In alternative embodiments, the guide wire candeliver radiofrequency or laser ablative energy to assist with traversalof tissue. However, in alternative embodiments, the distal end of theguide wire is bent to provide a J-shaped or a pigtail-shaped tip toprotect against perforation of tissue by the guide wire duringmanipulation. In still other alternative embodiments, the guide wireitself has a deflectable tip to facilitate traversal of tissueirrespective of natural tissue planes. One or more secondary catheterscan be deployed within the lumen of the guiding catheter. Like theguiding catheter, each secondary catheter has a proximal end and adistal end; however, not all secondary catheters have a lumen. Forexample, non-lumen secondary catheters can include various probes, suchas temperature probes, radiofrequency or cryogenic ablation probes, orsolid needles.

An exemplary non-limiting secondary catheter is a canalization needlecatheter, which can be deployed through the guiding catheter and into achamber of the heart to place cerclage annuloplasty ligature through thecoronary sinus around the mitral valve. A canalization-needle catheteris a type of secondary catheter that can be used to apply a suture to abodily tissue, organ, or structure of interest.

C. Application of Tension

Tension is applied via the annuloplasty cerclage through the sheathmaterial (e.g., 450), which is preferably a hollow braided suturematerial as described above. Tension can be applied to both ends of thesheath (e.g., 450) as they are externalized at the point of vascularaccess in concert with a lock delivery catheter as described in furtherdetail below that directs both ends of the suture through a lock mountedat the end of the lock delivery catheter.

In some procedures, it is possible for the ends of the tether 450 (theends of the implant that are externalized) to become twisted about eachother. This can complicate the delivery of the lock over the ends of thetether. To help ensure against this, after the ends of the tether 450are externalized (e.g, via the jugular or other access point), astraightening, or disentangling catheter 1900 as set forth in FIG. 19can be used to separate the ends of the tether so that they are paralleland not twisted, thereby greatly simplifying delivery of the lock overthe ends of the tether 450 into the heart. Catheter 1900 includes aplurality of snares 1901. In use, each end of tether 450 is fed into oneof the snares which terminates in a distal loop. Each snare can have abody made, for example from stainless steel wire or hypotube. Theproximal end of each snare is attached to a respective snare hub 1907,1908. Snares 1901 are slidably disposed through a dual lumen shaft 1902,made, for example, from Pebax material. A double hemostasis valve withgaskets 1903 is also provided at a proximal end of shaft 1902, and oneor more marker bands 1904 (e.g., of platinum-iridium), to help visualizethe location of the distal end of catheter 1900, are provided (held inplace by a heat shrink cover 1905 made of Pebax). A strain relief 1906is also provided that is heat shrunk about the proximal end of shaft1902. Various components can be held in place by suitable adhesives.After the tethers 450 are loaded into the catheter, the hubs 1907, 1908can be pulled proximally to advance dual lumen shaft 1902 into the bodyand down to the location in the heart where the lock is to be delivered.The operator can visualize the procedure under fluoroscopy, and canvisually detect locations where the tethers are twisted as long as thetethers 450 are radiopaque or include a radiopaque filament, such as aplatinum wire described elsewhere herein.

Once the tethers 450 are externalized and untangled, tension can beapplied under imaging guidance to the tethers through the lock at adistal end of the lock delivery catheter until the desired degree ofmitral annular circumferential reduction is accomplished, or until themitral valve regurgitation is reduced, or until other deleteriousendpoints are achieved such as mitral valve inflow obstruction. Tensionin the sheath (e.g., 450) can then be secured by locking the lock of thelock delivery catheter such as that described in copending U.S. patentapplication Ser. No. 14/074,517, filed Nov. 7, 2013, or the lockdelivery catheter described below. Alternatively, a knot may be tied andpushed through a guiding catheter. The lock or knot, as desired, can belocated at the right atrium or right ventricle where the two cerclagetrajectories cross, or at the point of vascular access, or in betweenthe two. Tension can thus be delivered, if desired, by counterpressureagainst the fixation device, for example, applied through a deliverycatheter. Before fixation, tension can be released or reduced, forexample, to reposition the protection device or to achieve a lowerdegree of mitral annular circumferential reduction.

As tension is applied, valvular regurgitation is preferably assessedrepeatedly and non-invasively by an appropriate imaging technique. Suchimaging techniques include X-ray angiography, electromagnetic positiondetection, MRI, external or intracavitary or intravascular ultrasound,X-ray computed tomography, pressure transducers in an affected chambersuch as the left atrium or the pulmonary vein or the pulmonary artery,or a “fusion” or combination of any of the above. After the valvularregurgitation has been reduced (or even eliminated) and a desiredtension is achieved, the tension is fixed using a lock or knot deliverysystem as mentioned above, and the excess sheath material proximal tothe lock or knot can be cut and removed in any desired manner. Inaccordance with one aspect of the disclosure a cutting instrument can beused as described further below with reference to FIGS. 14A-14I herein.

If the resulting circumferential sheath (e.g., 450) is knotted to form aclosed loop, the sheath 450 essentially becomes a cerclage suture.Without further elaboration, it is believed that one skilled in the artcan, using this description, utilize the present discoveries to theirfullest extent.

The use of the implant with protective device (e.g., 420) has beendisclosed for use in a cerclage annuloplasty technique. However, thedisclosed implants can be used with any other annuloplasty device thatextends even partially through the coronary sinus in a region thatcrosses an underlying coronary artery. For example, the protectivedevice (e.g., 420) can be used to protect against compression ofcoronary arteries with any coronary sinus annuloplasty device, such asthe coronary sinus device in U.S. Pat. No. 7,090,695 or the inflatablecoronary sinus device shown in U.S. patent Ser. No. 10/787,574 (U.S.Patent Publication No. 2004/0254600). Although these devices aredesigned for endovascular delivery, the protection device disclosedherein can also be used with annuloplasty devices that are implantedusing an open-chest surgical repair instead of a catheter basedapproach. The problem of coronary artery compression is also encounteredwith these devices, and the protective device disclosed herein may beused to avoid that problem. Hence the presently disclosed embodimentsare not limited to a protective device for use with cerclageannuloplasty, nor is it limited to use of the device with catheter baseddelivery techniques.

When used with a coronary sinus annuloplasty implant of any kind, theprotective device (e.g., 420) can be provided as an integral part of theimplant (e.g. 400) or as a separate device suitable for placementbetween the implant and an underlying coronary artery to be protected.When provided as an integral part of the implant, the implant ispositioned in the coronary sinus so that the arch of the support extendsover the underlying coronary artery. In alternative embodiments theprotection device can be provided as a separate device that is advancedthrough a catheter system until it is positioned over the coronaryartery to be protected.

A mitral cerclage annuloplasty device, as described herein, can pushheart tissue radially inwardly and create a retaining structureprojecting into the heart near the native mitral valve region to allowimplantation and securement of a prosthetic transcatheter mitral valve(TMV). As used herein, the terms prosthetic mitral valve, transcathetermitral valve, TMV, prosthetic mitral device, prosthetic mitral implant,and the like, include any prosthetic device implantable within oradjacent to the native mitral valve region, including valved devices andas well as devices that do not include a valve component (e.g., frames,stents, rings, fasteners, tethers, portions of a valved device, etc.).In some embodiments, cerclage annuloplasty can create an internal ridge,landing zone (as described herein above), fixation plane, etc. (referredto herein generally as a “retaining structure”) for a TMV to be secured.

The TMV secured to the retaining structure within the heart can comprisea radially compressible and radially expandable prosthetic device thatis delivered into the heart in a radially compressed state using atranscatheter, transvascular delivery approach, for example. Once insidethe heart, the TMV can expand, either using applied expansion force(e.g., an inflatable balloon) or using intrinsic self-expandingmaterials (e.g., nitinol) that cause the TMV to self-expand upon removalof a compressive force applied during delivery. Upon expansion, the TMVcan become secured to the retaining structure created by the mitralcerclage annuloplasty device to inhibit the TMV from migrating out ofposition within the heart. For example, the TMV can comprise a tubularframe that expands around both sides of the retaining structure and/orclamps onto the retaining structure.

When expanded, the implanted TMV can apply a radially outward force onthe heart tissue. This radially outward force can undesirably compressblood vessels in the heart tissue and cause constriction and reducedblood flow. At the same time, the radially inward force applied by themitral cerclage annuloplasty device can also undesirably compress bloodvessels in the heart tissue from the outside. This dual compression onthe cardiac blood vessels can exacerbate the risk of ischemia, heartattack, and other complications. Of particular concern are thecircumflex coronary artery and its marginal branches near the greatcardiac vein, which can between the implanted TMV and the surroundingmitral cerclage annuloplasty device. Accordingly, protection devices asdisclosed herein can help protect such blood vessels from compressionfrom both the outside-in (via the mitral cerclage annuloplasty device)and from inside-out (via the TMV).

FIG. 9 is a schematic cross-sectional view of the mitral valve region ofa heart showing an exemplary implant system 900 that includes animplanted TMV 912 positioned within the heart wall 902 and a mitralcerclage annuloplasty device 910 positioned around the heart wall. Thedevice 910 includes an arched protection device 420 spanning over acoronary artery 252 to protect the artery from compression applied byboth the device 910 from the outside and outward expansion force 914applied on the inside of the heart wall 902 by the TMV 912. Theexemplary protection device 420 includes an arched portion extendingbetween two flattened, generally coplanar proximal and distal segments428, 429. The bridge, or protective device 420 can have any combinationof features and dimensions described herein with regard to otherexemplary protection devices.

FIG. 10 shows a tensioning suture (e.g., 450) extending through thecoronary sinus 250 partially around the mitral valve without theinclusion of the disclosed protection device. Consequently, thecircumflex coronary artery 252 is entrapped under the tensioning sutureas the coronary sinus overlaps the artery, applying unwanted compressionon the artery. When a TMV is also implanted within the mitral valve, itcan apply additional inside-out compression force on the artery 252.Without the protection device, the artery 252 can collapse and/or bepinched by the opposing forces.

FIGS. 11A and 11B illustrate aspects of a lock delivery system inaccordance with the disclosure. For purposes of illustration, and notlimitation, the lock delivery system 1110 includes a delivery catheterhaving a proximal end and a distal end with a lock attached to itsdistal end. More specifically, lock delivery system 1110 includes anouter tubular member having an inner tubular member disposed therein.

The inner tubular member can be made from any suitable material,preferably a polymeric material such as PEEK. The outer tubular memberis preferably provided as a braided catheter material, such as apolymeric co-extrusion including a braided layer. The threadedconnection between fastener portion and inner tubular member permitsattachment of the two components to each other to thereby permit remoteopening and closing of the lock, as well as permitting the lock to beremoved and retrieved, if desired, even after full deployment of thelock. As depicted, this embodiment of a lock delivery system includes aproximal housing connected to a hemostatic delivery device hub withflush port connected to a distal outer tubular member that is connectedat its distal end to a housing for the lock body. The housing isconfigured and adapted to maintain the lock body in rotationalregistration with respect to the lock delivery system, such that turningthe delivery system will cause the lock body to turn with it. Device1110 further includes a rotatable release knob, or lever, 1154. When ina locked position, a tether routed around the distal end of device 1110is held fast and locked in place via frictional forces, holding the lockin place against the distal end of the device 1110. When the knob orlever 1154 is rotated by a predetermined amount about its rotation axiswithin the housing, such as 90 degrees, the tether is movable, andtension can be applied to the tether, if desired, or the tether can bewithdrawn from the device.

The illustrated embodiment of the lock delivery system further includesone or more additional spring loaded push buttons, or tension controls,for controlling grasping of either end of the outer sheath (e.g., 450)of the implant. In a default position where the button is not depressed,the tether passing through a capture mechanism associated with the pushbutton will grip the implant tether (e.g., sheath 450 describedelsewhere herein) and maintain it under tension. When each push button(individually and/or both) is pressed down, it will allow for release ofone or both tethers associated with the implant. It will be appreciatedthat both ends of the tether can be routed through the same controlbutton for purposes of simplicity.

As set forth in FIGS. 12A-12D, a further embodiment of a limb forattachment to a lock body in accordance with the present disclosure withan adjustable length is presented. FIG. 12D presents a cross sectionalview of an implant (e.g., tether 450) passing through a limb ofadjustable length that is attached at a proximal end to lock body 1212.The limb includes an outer tubular member 1260 that can include abell-shaped atraumatic distal tip 1266, preferably integral thereto, forabutting a septal wall. Outer tubular member 1260 is also preferablyattached to a distal section 1265 of an inner tubular member thatextends from the distal tip 1266 along a proximal direction to alocation where a compression spring 1264 is disposed underneath theouter tubular member 1260. The distal end of spring abuts the proximalend of the distal section 1265. A proximal inner tubular member 1262 isslidably disposed within a proximal section of tubular member 1260. Aproximal end of proximal inner tubular member 1262 is attached to thelock body 1212, and a distal end of the proximal inner tubular member1262 abuts a proximal end of the spring 1264. Thus, spring 1264 iscontained in a compartment defined by an inner cylindrical surface ofouter tubular member 1260 the proximal end of tubular member 1265 andthe distal end of tubular member 1262. Spring 1264 defines and surroundsan interior lumen along its length that permits the passage of sheath450.

In operation, when the distal tip 1266 abuts the septal wall, theoverall length of the limb can be reduced by pushing distally on thelock body, which in turn pushes against the proximal inner tubularmember 1262 that in turn slides distally within (and with respect to)the outer tubular member 1260, compressing the spring 1264. The proximalportion of inner tubular member 1262 that is not surrounded by outertubular member 1260 defines the amount that the spring can compress,which can be arranged as desired. The spring can be configured tocompress completely, or only partially. It will be appreciated that FIG.12D is a representative cross section, and is not intended to be todimensional scale. To further illustrate this embodiment, FIG. 12Aillustrates the limb in a lengthened state wherein the spring 1264 isnot compressed. FIG. 12B shows the spring partially compressed, and FIG.12C shows the spring fully compressed.

As set forth in FIGS. 12E-12H, a further embodiment of a limb with anadjustable length is presented. FIG. 12H presents a cross sectional view(not to dimensional scale) of an implant (e.g., tether 450) passingthrough a limb of adjustable length that is attached at a proximal endto lock body 1212. The limb includes an outer tubular member 1270 thatcan include a bell-shaped atraumatic distal tip 1276, preferablyintegral thereto, for abutting a septal wall. Outer tubular member 1270includes a distal section and a proximal section separated by acompression section 1272.

Compression section 1272 is defined by a plurality of parallel cutspassing from an outer surface of the outer tubular member to an innersurface of the outer tubular member. The cuts are arranged parallel to acentral longitudinal axis of the limb, and (preferably uniformly)distributed circumferentially around the circumference of the outertubular member 1270. The cuts are preferably of uniform length andlengthwise alignment (but this may be varied, as desired). Any suitablenumber of such cuts may be made around the tubular member 1270. Theproximal section of the outer tubular member may be directly attached tolock 1212. As illustrated, the proximal section of tubular member 1270is attached to a proximal section of an inner tubular member 1274,wherein the proximal end of tubular member 1274 is received within andattached to lock 1212. Tubular member 1274 is not attached to thesection of tubular member 1270 that is located distally of thecompression section 1272 to permit relative sliding contact between thetubular members 1270, 1274 in that section. In operation, and withreference to FIGS. 12E-12G, FIG. 12E illustrates the limb at fulllength, wherein the legs defined between the cuts in the compressionsection 1272 are beginning to separate from each other and bow radiallyoutwardly as the outer tubular member 1270 shortens. FIG. 12F shows thelegs bowed further outwardly as tubular member 1270 continues toshorten, and FIG. 12G shows member 1270 at its shortest length, whereinthe resilient legs of the “spring” or compression section 1272 are fullycompressed, forming a petal arrangement around the circumference of thelimb.

FIGS. 13A-3C illustrate deployment of the illustrated lock on theexemplary cerclage device in an animal. FIG. 13A illustrates an image ofthe lock delivery catheter 1110 delivered to a location where tensionmay be imposed on the sutures (e.g., 450) by pulling them proximallythrough the lock delivery system and locking the lock to maintain thetension. In FIG. 13B, the outer tubular member is released from theouter lock portion and withdrawn. In FIG. 13C, the inner tubular memberis attached from the inner portion of the lock, leaving the deployedlock in place, tensioning the cerclage implant.

FIGS. 14A-14I illustrate portions of a cutting instrument 1400 inaccordance with the disclosure for cutting the tethers/sheath materialafter the lock has been deployed. The cutting instrument 1400 includesan inner assembly with a blade that is slidably disposed within an outerassembly having a suture guide configured to hold suture/sheath materialin position to facilitate cutting thereof while inside the heart, orother intracorporeal location. FIG. 14A illustrates a distal portion ofthe inner assembly of the cutting instrument, which includes an elongatecore shaft member (attached at a proximal end to a push hub) to acutting blade holder at a distal end.

As illustrated in FIG. 14A, outer housing 1460 includes a rounded,atraumatic end 1466 and defines two axially spaced apart holestherethrough, wherein the distal hole 1464 accepts a sheath or suture(e.g., 450) therein as an entrance point or entrance hole, and theproximal hole 1462 provides an exit for the suture/sheath. In use, thecutting instrument 1400 is threaded over each tether of the implant inthis manner through the holes 1462, 1464 after the lock deliverycatheter is removed, and the sheath material (e.g., 450) is external tothe patient or otherwise easily accessible. The cutting instrument isthen delivered into the heart to a location near the lock that isalready in place. The inner assembly of the cutting mechanism is thenadvanced distally with respect to the outer assembly of the cuttingmechanism until the blade 1432 has advanced past both holes 1462, 1464,cutting the tether (e.g., 450) as illustrated in FIG. 14B. Asillustrated in FIG. 14C, the flattened distal profile of the cuttinginstrument 1400 both reduces the profile of the instrument, as well asprovide for superior alignment and smooth cutting operation. FIG. 14Dprovides a cutaway view of the distal end of the cutting instrumentshowing the relative placement of the inner and outer assemblies afterthe inner assembly has been fully extended distally to accomplish thecutting operation.

FIGS. 14E-14I illustrate use of the loading snare 1480. As illustratedin FIG. 22E, the catheter 1400 includes a distal end and internalmechanisms as set forth above, and including a proximal handle having aspring loaded push button trigger, wherein the button is biased in aproximal direction by the spring (not shown). The button is connected tothe inner movable shaft of the cutting catheter at the proximal end ofthe shaft, which is in turn connected at its distal end to the cuttingblade. When the button is depressed by a user, the blade advancesdistally past openings 1462, 1464 to cut any tether spanning theopenings through the cutting catheter 1400. The snare is utilized byinitially passing the elongate loop portion of the snare diagonallythrough the distal portion of catheter 1400 by way of openings 1462,1464. As illustrated in FIGS. 14G-14I, after the loop of snare 1480 ispositioned through catheter 1400, ends of loop tether/sheath 450 arepassed through the snare 1480, and the snare is withdrawn throughcatheter 1400, carrying tethers 450 therewith, effectuating threading ofthe cutting catheter with the loop tether/sheath 450.

It will be appreciated that other structures can be cut or severed usingthe cutting catheters of FIGS. 14A-14I. For example, in a furtherimplementation, the cutting catheter as disclosed can be used to cut acardiac lead previously attached to a pacemaker. Removal of cardiacleads is typically dangerous, but the presently disclosed embodiment canbe threaded down the cardiac lead, for example, into the left ventricleor other cardiac location. The lead can then be severed near or at theanchoring point, leaving the anchor in place, but removing the wire.

FIGS. 15A-15E illustrate a further embodiment of a lock deliverycatheter 1500 including a handle 1502 similar to previous embodiments.Catheter 1500 includes a handle 1502 that has the same functionality asprevious embodiments with a tensioning tether control as described abovewith reference to FIGS. 11A-11B. Catheter 1500 includes a lock releaseknob for advancing the lock mechanism proximally or distally withrespect to the handle 1502, as well as for releasably engaging the lockbody (e.g., via threaded connection) as set forth above. Catheter 1500further includes a removable sheath 1510 that surrounds the lock body1530, the coronary sinus limb 1540, the tricuspid valve limb 1550 thatmay include a bumper 1552 (for spreading out axial force applied to theseptal wall), and may provide a conduit for guiding placement of thetether loading snares. The catheter including the sheath 1510 can beintroduced into the patient's vasculature over the outer sheath (e.g.,450) of the implant after the delivery tubes (or core wires, dependingon the embodiment) are removed. The sheath can be withdrawn proximally,for example, via a pull wire (not shown) routed through handle 1502 orpeeled off, ruptured, or the like at a suitable time, such as when thedistal end of the sheath is near the patient's heart. The limbs are thenexposed, which can be directed into the vasculature of the heart, andplaced where desired. The sheath (e.g., 450) can then be locked insideof the lock body 1530, and the excess sheath extending proximally fromthe lock body 1530 can be severed using embodiments of the cuttingcatheter disclosed herein. FIG. 15C shows a schematic view of theinstalled implant and lock body with limbs, which may include thecoronary protection element 1580 (if desired) surrounded by the sheath1570, which may be radiopaque as discussed above. Also illustrated arethe tricuspid valve limb 1550 with the bumper 1552, as well as thecoronary sinus limb 1540. FIG. 15D presents an isometric view of thelock delivery system 1500 prior to deployment (release) of the lockbody, whereas FIG. 15E illustrates a perspective view of the lock andimplant after deployment. As illustrated, the limbs are presented as notbeing planar, but instead having a three dimensional curvature whereinthe limbs curve out of plane toward the lock. As will be appreciated,the proximal ends of the limbs are preferably attached to the lock body.

FIGS. 16A-16D illustrate a further embodiment of a lock body andprotruding limbs to be routed over the implant 400 during theimplantation procedure as described elsewhere herein. In particular,FIGS. 16A-16D detail the precise construction used to build thisembodiment. The limbs have a proximal end that attach to the lock body,and a distal end. As set forth in FIGS. 16A-16D, the proximal ends ofthe limbs are constructed by providing inner and outer concentricpolymeric tubes, wherein a distal end of a metallic (e.g., titanium)tube is inserted between the tubes at the proximal end of the tubes. Oneor more windows 1610, or holes, are defined in the portion of themetallic tube that is inserted between the tubes. The assembly is thenheated and formed in order to cause the polymeric material of the tubesto flow through the window(s) defined in the metallic tube, causing theinner and outer tubes to fuse to each other through the window(s) in thesidewall of the metallic tubular member. The opposing proximal end ofthe tubular member is then welded (e.g., laser welded) to the lock body(FIG. 16B). This procedure is used to form the proximal ends of bothlimbs and to attach them to the lock body. The metallic tubes and lockbody can be any suitable material (e.g., titanium, stainless steel,nickel-titanium alloys, and the like) formed, for example, into ahypotube. Preferably, the lock body and tubes are made from the same orsimilar materials to permit bonding by welding. As illustrated in FIG.16C, the polymeric limbs can be heat set to a shape that approximatesthe expected position of the device in the patient's anatomy. Thepolymeric limbs can be formed from polyether block amide or othersuitable material. FIG. 16D provides an illustrative cross section ofthe lock and limbs with the tether of the implant directed therethrough.

FIG. 17 presents a further embodiment of the lock and limb assembly,wherein the RVOT limb is illustrated as having interchangeable limbs1710 of different lengths to accommodate different sized vasculatures.Thus, a kit can be provided having limbs of varying lengths, and thepertinent medical professional can make an evaluation of which size limbextension to use. Limbs 1710 can be removably attached to the remainderof the structure, for example, by a threaded connection. It will beappreciated that the limb extensions can themselves be provided withfeatures as set forth elsewhere herein to provide adjustable length.

In accordance with further aspects, FIG. 18 illustrates animplementation 1800 of an implantable pacing system configured andarranged to circumnavigate a loop path in a heart. For example, U.S.Ser. No. 15/328,046 sets forth one technique for implanting a pacemakerlead via the septal vein using an approach through the coronary sinus,in a manner similar to making a path to implant devices in accordancewith the present disclosure. Thus, an initial lead (preferably a bipolarlead) is anchored in the septal wall in a location where signalsoriginating therefrom can provide a minimum QRS. Once suitably anchored,if desired, a proximal end of the lead, or an extension thereof, can beexternalized from the patient, and a specially configured implantsimilar in structure to implant 400 can be delivered over the cardiaclead, using the cardiac lead as a delivery rail at least in part.Alternatively, the lead can be externalized, and the implant can bedelivered after being crimped to a proximal end of an externalizedguidewire as disclosed herein, and the implant can be installed. When itcomes time to install the lock, the lock can be threaded over theimplant (e.g., 400) as well as the cardiac lead, and when the lock islocked in place, the lock can be configured to complete an electricalcontact with the lead. For example, the lock can include a controllerhaving a power supply and a signal generator. The inner elongate tethercan also be caused to complete an electrical circuit with the lock, andappropriate control circuitry can be provided in the lock for the loopof platinum or other wire in the inner tether to function as an antennafor sending or receiving signals, or for receiving a charging pulse tocharge a battery in the lock for powering the pacemaker.

However, embodiment 1800 can also be configured to contain all of itssensors and electrodes (referred to in combination as 1820) on board.Thus, the implant 1800 can be delivered and assembled in place, and canbe programmed to stimulate cardiac tissue and/or sense biologicalconditions (e.g., electrical mechanical and chemical conditions) withinthe heart.

Thus, the pacing system 1800 can include an elongate inner tether as setforth herein having a proximal end and a distal end, an outer sheathmaterial surrounding the elongate inner tether having a proximal end anda distal end, at least one electrical conductor disposed along or withinat least one of the elongate inner tether and the outer sheath, acardiac pacing controller 1810, which may be integrated into the lock ofthe implant, may include a power source, a pulse generator, and controlcircuitry operably coupled to the at least one electrical conductor, atleast one cardiac pacing electrode configured and arranged to beimplanted in or on top of cardiac tissue, the at least one cardiacpacing electrode being electrically coupled to the cardiac pacingcontroller by way of the at least one electrical conductor, and a locksecuring the proximal end and distal end of the outer sheath material.

In some implementations, the lock can be coupled to the cardiac pacingcontroller. The at least one electrical conductor is disposed at leastpartially within the elongate inner tether. If desired, thelock/controller 1810 can include one or more cardiac pacing leads routedtherethrough terminating at electrodes indicated a locations 1820, orany other desired location. Electrical communication can be establishedwith the cardiac pacing lead by engaging a portion of the lock. Or, thelock/controller 1810 can be pre-connected to cardiac leads andelectrodes integrally formed into the curved tubular limbs of theimplant that connect to the lock/controller 1810. If desired, theportion 400 of the implant received by the lock limbs can also beprovided with sensors 820. If desired, electrical power can be directlytransferred to implant 400 via a core platinum wire described elsewhereherein. Components integrated into the portion 400, such as sensors andelectrodes, can then draw power off of the core wire (e.g., 410 a′) inorder to operate. Electrical connections between the power supply/lock1810 and pacing electrodes 1820 or other sensors can be directconductive pathways wherein conductors are placed between inner andouter tubular polymeric layers of the limbs attached to thelock/controller 1820, or nested within the layers of the implant 400. Ifdesired, the sensors or electrodes can be formed over the surface of theimplant lock/limbs and portion 400, and then be overlaid with anadditional layer of heat shrunk polymeric tubing. If desired, that outerlayer of tubing can include windows formed therein for exposing thesensors or electrodes 1820.

In some implementations, the pacing system 1800 can further include atleast one lumen along a length of the outer sheath for receiving apacing lead, wherein the pacing system can be slid along the pacing leadinto the coronary sinus. The at least one lumen can be configured todirect the pacing lead toward the cardiac pacing controller. In someembodiments, the system can include a protective bridge for spanning theLCx artery when in the coronary sinus near the septal wall as describedelsewhere herein. In some embodiments, at least a portion of the cardiacpacing controller can be disposed within the outer sheath.

The pacing system can further include an electrical battery disposedwithin components 1810 and/or 400 that is at least partially disposedwithin the outer sheath. The pacing system can further include a circuitboard that is at least partially disposed within the outer sheath. Thepacing system can further include communications circuitry that is atleast partially disposed within the outer sheath. The communicationscircuitry can be hard wired, and/or wireless (e.g., via Bluetoothcommunication).

If desired, the pacing system 1800 can further include at least onesensor circuit that is at least partially disposed within the outersheath, the at least one sensor module 1820 including at least onesensor (e.g., sensing circuitry) for sensing at least one biologicalparameter. For example, the at least one sensor circuit/module caninclude at least one pressure sensor for detecting blood pressure, or atleast one of a chemical sensor, a distance sensor, a sensor havingcircuitry to detect electro physiological data, a movement sensor, and alocation sensor.

In some implementations, the at least one electrical conductor canterminate at the lock/controller 1810. If desired, the system canfurther include at least one pacing lead (and/or electrical sensor forsensing cardiac electrical signals) formed into a surface of the outersheath. The at least one pacing lead can be configured and arranged tointerface with the Right Atrium. If desired, a further pacing lead canbe configured and arranged to interface with the Right Ventricle, or acardiac vein such as the septal vein, and be located, for example, inthe regions denoted by circles in FIG. 18. If desired, the controller1810 can be configured and arranged to provide at least one of pacing,defibrillation, measurement and control.

In some implementations of the pacing system the inner elongate tethercan include a loop antenna that conducts signals to and from thecontroller. In further implementations, the pacing system (or othersystem) can further include a reservoir for containing a beneficialagent coupled to a dispenser controlled by the controller. For example,the beneficial agent can include a medication, a gene therapy material,and/or living cells for seeding at least one location of the heart thatis damaged.

The heart's intrinsic electrical activity (i.e. the P wave or QRScomplex) transmits a small electrical current (a few millivolts),through the pacemaker leads, to the pulse generator. This current can beregistered or sensed by the pacemaker circuitry. The pacemaker sensingcan be used to formulate a response of a pacemaker to intrinsicheartbeats. The P waves, or atrial activity, are transmitted through anatrial lead (if present) to an atrial channel of the pacemaker, andsensed as atrial activity. Ventricular activity (the QRS complex) can betransmitted through the ventricular lead (if present, such as via theseptal vein) to the ventricular channel of the pacemaker, and this issensed as ventricular activity.

For electrical activity to be transmitted from the heart to thepacemaker, a closed electrical circuit must be present, just the same asfor an electrical impulse to be transmitted from the pacemaker to theheart. Thus, just as with pacing, sensing can be unipolar or bipolar.Bipolar sensing detects the intrinsic electrical activity occurringbetween the tip electrode and the ring electrode of the lead. Unipolarsensing detects electrical activity occurring between the tip of thelead, and the metal shell of the pulse generator. Because this is a muchlarger area, other electrical signals, such as might be generated by themuscles of the diaphragm or sources outside the body, are more likely tobe detected (and therefore incorrectly interpreted by the pacemaker asheart beats). It is important to note that the only way the pacemakercan determine which chamber a signal originates from is by which leadtransmits the signal to the pacemaker. For example, the pacemaker couldinterpret any electrical signal transmitted through the atrial lead tothe atrial channel as a P wave, even if the signal is in fact a QRScomplex large enough in amplitude to be sensed by the atrial channelNote also that the time at which the pacemaker senses the atrial orventricular signal is not necessarily the beginning of the P wave orQRS. The pacemaker cannot sense activity in a chamber until theelectrical activity actually reaches the pacemaker lead.

The devices and methods disclosed herein can be used for otherprocedures in an as-is condition, or can be modified as needed to suitthe particular procedure. In view of the many possible embodiments towhich the principles of this disclosure may be applied, it should berecognized that the illustrated embodiments are only preferred examplesof the disclosure and should not be taken as limiting the scope of thedisclosure. Each and every patent and patent application referencedherein is expressly incorporated by reference herein in its entirety forany purpose whatsoever.

The invention claimed is:
 1. A snare catheter, comprising: a) anelongate core member having a proximal end and a distal end; b) anelongate intermediate tubular member having a proximal end, a distal endand defining an elongate lumen therethrough for slidably receiving theelongate core member therein; c) a collapsible tubular perforated bodyformed from a plurality of elongate filaments attached at a proximal endthereof to the distal end of the elongate intermediate tubular member,and at a distal end thereof to the distal end of the elongate coremember, wherein relative axial displacement of the distal end of theelongate intermediate tubular member toward the distal end of theelongate core member causes the collapsible tubular perforated body toexpand radially outwardly and for the elongate filaments to mutuallyseparate, and relative axial displacement of the distal end of theelongate intermediate tubular member away from the distal end of theelongate core member causes the collapsible tubular perforated body tocollapse radially inwardly and for the elongate filaments members tocollapse together; d) a target wire disposed within the collapsibletubular perforated body that extends along the elongate core member andhas a proximal end attached to the elongate intermediate tubular memberand a distal end attached to the elongate core member, wherein thetarget wire is configured to assume a first generally straightconfiguration when the collapsible tubular perforated body is collapsedradially inwardly, and a second substantially nonlinear configurationwhen the collapsible tubular perforated body is expanded radiallyoutwardly; and e) an elongate tubular longitudinally displaceable sheathhaving a proximal end, a distal end and defining an elongate lumentherethrough for slidably receiving the elongate core member, elongateintermediate tubular member, collapsible tubular perforated body, andtarget wire therein when the collapsible tubular perforated body is in agenerally radially collapsed state.
 2. The snare catheter of claim 1,wherein the elongate core member is a tubular member defining aguidewire lumen therethrough.
 3. The snare catheter of claim 1, furthercomprising an atraumatic distal tip formed from compliant material thatis attached to the distal end of the elongate core member to facilitatepassage through tortuous anatomy.
 4. The snare catheter of claim 1,further comprising radiopaque marker bands disposed near the distal endof the catheter and the distal end of the elongate intermediate tubularmember.
 5. The snare catheter of claim 1, further comprising a pluralityof radiopaque marker bands formed on the target wire.
 6. The snarecatheter of claim 1, wherein the target wire is formed at least in partfrom radiopaque material.
 7. The snare catheter of claim 1, wherein thecollapsible tubular perforated body is formed at least in part fromradiopaque material.
 8. The snare catheter of claim 1, wherein thetarget wire includes at least one loop formed therein when it islongitudinally contracted.
 9. The snare catheter of claim 1, wherein thetarget wire includes a plurality of loops formed therein when it islongitudinally contracted.
 10. The snare catheter of claim 8, whereinthe target wire and loop substantially lay in a single plane parallel toa longitudinal axis of the catheter when the target wire islongitudinally contracted.
 11. The snare catheter of claim 8, whereinthe target wire and loop define a three dimensional geometry when thetarget wire is longitudinally contracted.
 12. The snare catheter ofclaim 1, further comprising a second target wire, wherein the targetwire each define at least one loop therein when the target wires arelongitudinally contracted.
 13. The snare catheter of claim 1, whereinthe target wire includes at least one undulation formed therein when itis longitudinally contracted.
 14. The snare catheter of claim 13,wherein the target wire substantially lays in a single plane parallel toa longitudinal axis of the catheter when the target wire islongitudinally contracted.
 15. The snare catheter of claim 13, whereinthe target wire substantially defines a three dimensional geometry whenthe target wire is longitudinally contracted.
 16. The snare catheter ofclaim 1, wherein the target wire includes composite wire.
 17. The snarecatheter of claim 1, wherein the target wire includes a core portionmade from a first material, and a cladding portion made from a secondmaterial different from the first material.